Medical Hypotheses
Volume 56, Issue 2 , Pages 137-154 , February 2001

Current prospects for controlling cancer growth with non-cytotoxic agents – nutrients, phytochemicals, herbal extracts, and available drugs

Received 24 November 1999 ,Accepted 15 March 2000.

References 

    REFERENCES
  1. Baserga R, Porcu P, Rubini M, Sell C. Cell cycle control by the IGF-1 receptor and its ligands. Adv Exp Med Biol. 1993;343:105–112
  2. Resnicoff M, Abraham D, Yutanawiboonchai W, Rotman HL, Kajstura J, Rubin R. The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res. 1995;55:2463–2469
  3. Parrizas M, Saltiel AR, LeRoith D. Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3’-kinase and mitogen-activated protein kinase pathways. J Biol Chem. 1997;272:154–161
  4. Baserga R, Resnicoff M, Dews M. The IGF-I receptor and cancer. Endocrine. 1997;7:99–102
  5. Prisco M, Romano G, Peruzzi F, Valentinis B, Baserga R. Insulin and IGF-I receptors signaling in protection from apoptosis. Horm Metab Res. 1999;31:80–89
  6. Werner H, LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996;68:183–223
  7. Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors. Endocr Rev. 1994;15:80–101
  8. Underwood LE, Thissen JP, Lemozy S, Ketelslegers JM, Clemmons DR. Hormonal and nutritional regulation of IGF-I and its binding proteins. Horm Res. 1994;42:145–151
  9. Goldstein S, Harp JB, Phillips LS. Nutrition and somatomedin. XXII: Molecular regulation of insulin-like growth factor-I during fasting and refeeding in rats. J Mol Endocrinol. 1991;6:33–43
  10. Harp JB, Goldstein S, Phillips LS. Nutrition and somatomedin. XXIII. Molecular regulation of IGF-I by amino acid availability in cultured hepatocytes. Diabetes. 1991;40:95–101
  11. Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994;42:140–144
  12. Suikkari AM, Koivisto VA, Rutanen EM, Yki-Jarvinen H, Karonen SL, Seppala M. Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J Clin Endocrinol Metab. 1988;66:266–272
  13. Snyder DK, Clemmons DR. Insulin-dependent regulation of insulin-like growth factor-binding protein-1. J Clin Endocrinol Metab. 1990;71:1632–1636
  14. Lee PD, Conover CA, Powell DR. Regulation and function of insulin-like growth factor-binding protein-1. Proc Soc Exp Biol Med. 1993;204:4–29
  15. Kato H, Umezawa T, Miura Y, Noguchi T. The effect of quantity and nutritional quality of dietary proteins on plasma concentration of insulin-like growth factor binding proteins (IGFBP) and the saturability of IGFBP with endogeneous IGF-I. Adv Exp Med Biol. 1991;293:171–178
  16. Straus DS, Burke EJ, Marten NW. Induction of insulin-like growth factor binding protein-1 gene expression in liver of protein-restricted rats and in rat hepatoma cells limited for a single amino acid. Endocrinology. 1993;132:1090–1100
  17. Jousse C, Bruhat A, Ferrara M, Fafournoux P. Physiological concentration of amino acids regulates insulin-like-growth-factor-binding protein 1 expression. Biochem J. 1998;334:147–153
  18. Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr. 1999;129:1628–1635
  19. Mukherjee P, Sotnikov AV, Mangian HJ, Zhou JR, Visek WJ, Clinton SK. Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression [see comments]. J Natl Cancer Inst. 1999;91:512–523
  20. Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 1997;57:4667–4672
  21. Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB. Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem. 1996;271:29483–29488
  22. Punglia RS, Lu M, Hsu J, Kuroki M, Tolentino MJ, Keough K. Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. Diabetes. 1997;46:1619–1626
  23. Zelzer E, Levy Y, Kahana C, Shilo BZ, Rubinstein M, Cohen B. Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1 alpha/ARNT. EMBO J. 1998;17:5085–5094
  24. Akagi Y, Liu W, Zebrowski B, Xie K, Ellis LM. Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res. 1998;58:4008–4014
  25. Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D, Adami HO. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia [see comments]. Br J Cancer. 1997;76:1115–1118
  26. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study [see comments]. Science. 1998;279:563–566
  27. Wolk A, Mantzoros CS, Andersson SO, Bergstrom R, Signorello LB, Lagiou P. Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study [see comments]. J Natl Cancer Inst. 1998;90:911–915
  28. Tricoli JV, Winter DL, Hanlon AL, Raysor SL, Watkins-Bruner D, Pinover WH. Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer. Urology. 1999;54:178–182
  29. Pollak M, Beamer W, Zhang JC. Insulin-like growth factors and prostate cancer. Cancer Metastasis Rev. 1998;17:383–390
  30. Ng EH, Ji CY, Tan PH, Lin V, Soo KC, Lee KO. Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients. Ann Surg Oncol. 1998;5:194–201
  31. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer [see comments]. Lancet. 1998;351:1393–1396
  32. Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS. Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology. 1998;9:570–573
  33. Stoll BA. Western nutrition and the insulin resistance syndrome: a link to breast cancer. Eur J Clin Nutr. 1999;53:83–87
  34. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3 [see comments]. J Natl Cancer Inst. 1999;91:620–625
  35. Manousos O, Souglakos J, Bosetti C, Tzonou A, Chatzidakis V, Trichopoulos D. IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer. 1999;83:15–17
  36. Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X. Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Natl Cancer Inst. 1999;91:151–156
  37. Suwanichkul A, DePaolis LA, Lee PD, Powell DR. Identification of a promoter element which participates in cAMP-stimulated expression of human insulin-like growth factor-binding protein-1. J Biol Chem. 1993;268:9730–9736
  38. Kachra Z, Yang CR, Murphy LJ, Posner BI. The regulation of insulin-like growth factor-binding protein 1 messenger ribonucleic acid in cultured rat hepatocytes: the roles of glucagon and growth hormone [see comments]. Endocrinology. 1994;135:1722–1728
  39. Lewitt MS, Denyer GS, Cooney GJ, Baxter RC. Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology. 1991;129:2254–2256
  40. McCarty MF. Vegan proteins may reduce risk for cancer, obesity, and cardiovascular disease by promoting increased glucagon activity. Med Hypotheses. 1999;
  41. McCarty MF. Dietary glycemic index may influence cancer risk by modulating IGF-I activity: a hypothesis. J Medicinal Food. 1998;1:123–140
  42. Truswell AS. Glycaemic index of foods. Eur J Clin Nutr. 1992;46:S91–S101
  43. Rabinowitz D, Merimee TJ, Maffezzoli R, Burgess JA. Patterns of hormonal release after glucose, protein, and glucose plus protein. Lancet. 1966;2:454–456
  44. Slabber M, Barnard HC, Kuyl JM, Dannhauser A, Schall R. Effects of a low-insulin-response, energy-restricted diet on weight loss and plasma insulin concentrations in hyperinsulinemic obese females. Am J Clin Nutr. 1994;60:48–53
  45. Remer T, Pietrzik K, Manz F. A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion of dehydroepiandrosterone sulfate. Metabolism. 1996;45:1483–1486
  46. Barnard RJ, Ugianskis EJ, Martin DA, Inkeles SB. Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. Am J Cardiol. 1992;69:440–444
  47. Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med. 1998;49:235–261
  48. Anderson RA, Cheng N, Bryden NA, Polansky MM, Chi J, Feng J. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes. Diabetes. 1997;46:1786–1791
  49. Cefalu WT, Bell-Farrow AD, Wang ZQ. The effect of chromium supplementation on carbohydrate metabolism and body composition. Diabetes. 1997;46:55A
  50. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metaformin in non-insulin-dependent diabetes mellitus [see comments]. N Engl J Med. 1995;333:550–554
  51. Spence JT, Koudelka AP. Effects of biotin upon the intracellular level of cGMP and the activity of glucokinase in cultured rat hepatocytes. J Biol Chem. 1984;259:6393–6396
  52. Maebashi M, Makino Y, Furukawa Y. Therapeutic evaluation of the effect of biotin on hyperglycemia in patients with non-insulin-dependent diabetes mellitus. J Clin Biochem Nutr. 1993;14:211–218
  53. McCarty MF. High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy of type II diabetes. Med Hypotheses. 1999;
  54. Campbell TC, Junshi C. Diet and chronic degenerative diseases: perspectives from China. Am J Clin Nutr. 1994;59:1153S–1161S
  55. Kurowska EM, Carroll KK. Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits. Biochim Biophys Acta. 1992;1126:185–191
  56. Sanchez A, Hubbard RW, Smit E, Hilton GF. Testing a mechanism of control in human cholesterol metabolism: relation of arginine and glycine to insulin and glucagon. Atherosclerosis. 1988;71:87–92
  57. Sanchez A, Hubbard RW, Hilton GF. Hypocholesterolemic amino acids and the insulin glucagon ratio. Monogr Atheroscler. 1990;16:126–138
  58. Sanchez A, Hubbard RW. Plasma amino acids and the insulin/glucagon ratio as an explanation for the dietary protein modulation of atherosclerosis. Med Hypotheses. 1991;36:27–32
  59. Carter JP, Saxe GP, Newbold V, Peres CE, Campeau RJ, Bernal-Green L. Hypothesis: dietary management may improve survival from nutritionally linked cancers based on analysis of representative cases. J Am Coll Nutr. 1993;12:209–226
  60. Foster-Powell K, Miller JB. International tables of glycemic index. Am J Clin Nutr. 1995;62:871S–890S
  61. Holt SH, Miller JC, Petocz P. An insulin index of foods: the insulin demand generated by 1000-kJ portions of common foods. Am J Clin Nutr. 1997;66:1264–1276
  62. Gates JR, Parpia B, Campbell TC, Junshi C. Association of dietary factors and selected plasma variables with sex hormone-binding globulin in rural Chinese women. Am J Clin Nutr. 1996;63:22–31
  63. Granfeldt Y, Bjorck I, Hagander B. On the importance of processing conditions, product thickness and egg addition for the glycaemic and hormonal responses to pasta: a comparison with bread made from ‘pasta ingredients’. Eur J Clin Nutr. 1991;45:489–499
  64. McTiernan A, Ulrich C, Slate S, Potter J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control. 1998;9:487–509
  65. Carroll KK. Obesity as a risk factor for certain types of cancer. Lipids. 1998;33:1055–1059
  66. Helle SI, Omsjo IH, Hughes SC, Botta L, Huls G, Holly JM. Effects of oral and transdermal oestrogen replacement therapy on plasma levels of insulin-like growth factors and IGF binding proteins 1 and 3: a cross-over study. Clin Endocrinol (Oxf). 1996;45:727–732
  67. O’Sullivan AJ, Crampton LJ, Freund J, Ho KK. The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women. J Clin Invest. 1998;102:1035–1040
  68. Ho GH, Ji CY, Phang BH, Lee KO, Soo KC, Ng EH. Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study. Ann Surg Oncol. 1998;5:361–367
  69. Corsello SM, Rota CA, Putignano P, Della CS, Barnabei A, Migneco MG. Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer. Eur J Endocrinol. 1998;139:309–313
  70. Decensi A, Robertson C, Ballardini B, Paggi D, Guerrieri-Gonzaga A, Bonanni B. Effect of tamoxifen on lipoprotein(a) and insulin-like growth factor-I (IGF-I) in healthy women. Eur J Cancer. 1999;35:596–600
  71. Chute CG, Willett WC, Colditz GA, Stampfer MJ, Rosner B, Speizer FE. A prospective study of reproductive history and exogenous estrogens on the risk of colorectal cancer in women [see comments]. Epidemiology. 1991;2:201–207
  72. Newcomb PA, Storer BE. Postmenopausal hormone use and risk of large-bowel cancer [see comments] [published erratum appears in J Natl Cancer Inst 1995 Sep 20; 87(18): 1416]. J Natl Cancer Inst. 1995;87:1067–1071
  73. Calle EE, Miracle-McMahill HL, Thun MJ, Heath CWJ. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. J Natl Cancer Inst. 1995;87:517–523
  74. Ettinger B, Friedman GD, Bush T, Quesenberry CPJ. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol. 1996;87:6–12
  75. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet. 1993;342:1209–1210
  76. Poirot M, Chailleux C, Fargin A, Bayard F, Faye JC. A potent and selective photoaffinity probe for the anti-estrogen binding site of rat liver. J Biol Chem. 1990;265:17039–17043
  77. Yin F, Giuliano AE, Van Herle AJ. Growth inhibitory effects of flavonoids in human thyroid cancer cell lines. Thyroid. 1999;9:369–376
  78. Doyle JW, Kandutsch AA. Requirement for mevalonate in cycling cells: quantitative and temporal aspects. J Cell Physiol. 1988;137:133–140
  79. Jakobisiak M, Bruno S, Skierski JS, Darzynkiewicz Z. Cell cycle-specific effects of lovastatin. Proc Natl Acad Sci USA. 1991;88:3628–3632
  80. Keyomarsi K, Sandoval L, Band V, Pardee AB. Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res. 1991;51:3602–3609
  81. Langan TJ, Slater MC. Isoprenoids and astroglial cell cycling: diminished mevalonate availability and inhibition of dolichol-linked glycoprotein synthesis arrest cycling through distinct mechanisms. J Cell Physiol. 1991;149:284–292
  82. Larsson O. Cell cycle-specific growth inhibition of human breast cancer cells induced by metabolic inhibitors. Glycobiology. 1993;3:475–479
  83. Naderi S, Blomhoff R, Myklebust J, Smeland EB, Erikstein B, Norum KR. Lovastatin Inhibits G1/S Transition of Normal Human B-Lymphocytes Independent of Apoptosis. Exp Cell Res. 1999;252:144–153
  84. Kabakoff BD, Doyle JW, Kandutsch AA. Relationships among dolichyl phosphate, glycoprotein synthesis, and cell culture growth. Arch Biochem Biophys. 1990;276:382–389
  85. Carlberg M, Dricu A, Blegen H, Wang M, Hjertman M, Zickert P. Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth. J Biol Chem. 1996;271:17453–17462
  86. Dricu A, Wang M, Hjertman M, Malec M, Blegen H, Wejde J. Mevalonate-regulated mechanisms in cell growth control: role of dolichyl phosphate in expression of the insulin-like growth factor-1 receptor (IGF-1R) in comparison to Ras prenylation and expression of c- myc. Glycobiology. 1997;7:625–633
  87. Dricu A, Carlberg M, Wang M, Larsson O. Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res. 1997;57:543–548
  88. Vogt A, Sun J, Qian Y, Hamilton AD, Sebti SM. The geranylgeranyltransferase-I inhibitor GGTI-298 arrests human tumor cells in G0/G1 and induces p21 (WAF1/CIP1/SD11) in a p53-independent manner. J Biol Chem. 1997;272:27224–27229
  89. Casey PJ, Seabra MC. Protein prenyltransferases. J Biol Chem. 1996;271:5289–5292
  90. Rubin R, Baserga R. Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis, and tumorigenicity. Lab Invest. 1995;73:311–331
  91. Dricu A, Kanter L, Wang M, Nilsson G, Hjertman M, Wejde J. Expression of the insulin-like growth factor 1 receptor (IGF-1R) in breast cancer cells: evidence for a regulatory role of dolichyl phosphate in the transition from an intracellular to an extracellular IGF-1 pathway. Glycobiology. 1999;9:571–579
  92. Parker RA, Pearce BC, Clark RW, Gordon DA, Wright JJ. Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3- methylglutaryl-coenzyme A reductase. J Biol Chem. 1993;268:11230–11238
  93. Elson CE, Yu SG. The chemoprevention of cancer by mevalonate-derived constituents of fruits and vegetables. J Nutr. 1994;124:607–614
  94. Case GL, He L, Mo H, Elson CE. Induction of geranyl pyrophosphate pyrophosphatase activity by cholesterol-suppressive isoprenoids. Lipids. 1995;30:357–359
  95. Elson CE. Suppression of mevalonate pathway activities by dietary isoprenoids: protective roles in cancer and cardiovascular disease. J Nutr. 1995;125:1666S–1672S
  96. He L, Mo H, Hadisusilo S, Qureshi AA, Elson CE. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr. 1997;127:668–674
  97. Elson CE, Peffley DM, Hentosh P, Mo H. Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer. Proc Soc Exp Biol Med. 1999;221:294–311
  98. Harrison LE, Wojciechowicz DC, Brennan MF, Paty PB. Phenylacetate inhibits isoprenoid biosynthesis and suppresses growth of human pancreatic carcinoma. Surgery. 1998;124:541–550
  99. Sebti SM, Hamilton AD. Inhibition of Ras prenylation: a novel approach to cancer chemotherapy. Pharmacol Ther. 1997;74:103–114
  100. Qian Y, Sebti SM, Hamilton AD. Farnesyltransferase as a target for anticancer drug design. Biopolymers. 1997;43:25–41
  101. Narisawa T, Fukaura Y, Terada K, Umezawa A, Tanida N, Yazawa K. Prevention of 1,2-dimethylhydrazine-induced colon tumorigenesis by HMG-CoA reductase inhibitors, pravastatin and simvastatin, in ICR mice. Carcinogenesis. 1994;;15:2045–2048
  102. Soma MR, Baetta R, De Renzis MR, Mazzini G, Davegna C, Magrassi L. In vivo enhanced antitumor activity of carmustine [N,N’-bis(2-chloroethyl)-N-nitrosourea] by simvastatin. Cancer Res. 1995;55:597–602
  103. Hawk MA, Cesen KT, Siglin JC, Stoner GD, Ruch RJ. Inhibition of lung tumor cell growth in vitro and mouse lung tumor formation by lovastatin. Cancer Lett. 1996;109:217–222
  104. Inano H, Suzuki K, Onoda M, Wakabayashi K. Anti- carcinogenic activity of simvastatin during the promotion phase of radiation-induced mammary tumorigenesis of rats. Carcinogenesis. 1997;18:1723–1727
  105. Feleszko W, Zagozdzon R, Golab J, Jakobisiak M. Potentiated antitumour effects of cisplatin and lovastatin against MmB16 melanoma in mice. Eur J Cancer. 1998;34:406–411
  106. Clutterbuck RD, Millar BC, Powles RL, Newman A, Catovsky D, Jarman M. Inhibitory effect of simvastatin on the proliferation of human myeloid leukaemia cells in severe combined immunodeficient (SCID) mice. Br J Haematol. 1998;102:522–527
  107. Feleszko W, Balkowiec EZ, Sieberth E, Marczak M, Dabrowska A, Giermasz A. Lovastatin and tumor necrosis factor-alpha exhibit potentiated antitumor effects against Ha- ras-transformed murine tumor via inhibition of tumor-induced angiogenesis. Int J Cancer. 1999;81:560–567
  108. Thibault A, Samid D, Tompkins AC, Figg WD, Cooper MR, Hohl RJ. Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clin Cancer Res. 1996;2:483–491
  109. Qureshi AA, Qureshi N, Wright JJ, Shen Z, Kramer G, Gapor A. Lowering of serum cholesterol in hypercholesterolemic humans by tocotrienols (palmvitee). Am J Clin Nutr. 1991;53:1021S–1026S
  110. Qureshi AA, Bradlow BA, Brace L, Manganello J, Peterson DM, Pearce BC. Response of hypercholesterolemic subjects to administration of tocotrienols. Lipids. 1995;30:1171–1177
  111. He L, Mo H, Hadisusilo S, Qureshi AA, Elson CE. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr. 1997;127:668–674
  112. Elson CE, Peffley DM, Hentosh P, Mo H. Isoprenoid- mediated inhibition of mevalonate synthesis: potential application to cancer. Proc Soc Exp Biol Med. 1999;221:294–311
  113. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst. 1999;91:317–331
  114. Narisawa T, Fukaura Y, Hasebe M, Nomura S, Oshima S, Sakamoto H. Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene. Jpn J Cancer Res. 1998;89:1003–1008
  115. Okajima E, Tsutsumi M, Ozono S, Akai H, Denda A, Nishino H. Inhibitory effect of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4- hydroxybutyl)nitrosamine initiation. Jpn J Cancer Res. 1998;89:22–26
  116. Sharoni Y, Giron E, Rise M, Levy J. Effects of lycopene-enriched tomato oleoresin on 7,12-dimethyl- benz[a]anthracene-induced rat mammary tumors. Cancer Detect Prev. 1997;21:118–123
  117. Fuhrman B, Elis A, Aviram M. Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. Biochem Biophys Res Commun. 1997;233:658–662
  118. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer. 1995;24:257–266
  119. Thibault A, Samid D, Cooper MR, Figg WD, Tompkins AC, Patronas N. Phase I study of phenylacetate administered twice daily to patients with cancer. Cancer. 1995;75:2932–2938
  120. Gould MN. Cancer chemoprevention and therapy by monoterpenes. Environ Health Perspect. 1997;105 Suppl 4:977–979
  121. Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J Nutr. 1999;129:775S–778S
  122. Karlson J, Borg-Karlson AK, Unelius R, Shoshan MC, Wilking N, Ringborg U. Inhibition of tumor cell growth by monoterpenes in vitro: evidence of a Ras-independent mechanism of action. Anticancer Drugs. 1996;7:422–429
  123. Ren Z, Elson CE, Gould MN. Inhibition of type I and type II geranylgeranyl-protein transferases by the monoterpene perillyl alcohol in N1H3T3 cells. Biochem Pharmacol. 1997;54:113–120
  124. Hardcastle IR, Rowlands MG, Barber AM, Grimshaw RM, Mohan MK, Nutley BP. Inhibition of protein prenylation by metabolites of limonene. Biochem Pharmacol. 1999;57:801–809
  125. Nagourney RA. Oral limonene: combined prenylation inhibitor therapy of cancer. J Medicinal Food. 1998;1:83–88
  126. Lowy DR, Willumsen BM. Function and regulation of ras. Annu Rev Biochem. 1993;62:851–891
  127. Bos JL. ras oncogenes in human cancer: a review [published erratum appears in Cancer Res 1990 Feb 15 50(4):1352],. Cancer Res. 1989;49:4682–4689
  128. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ. Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice [see comments]. Nat Med. 1995;1:792–797
  129. Banerjee DK, Vendrell-Ramos M. Is asparagine-linked protein glycosylation an obligatory requirement for angiogenesis?. Indian J Biochem Biophys. 1993;30:389–394
  130. Banerjee DK. Angiogenesis: characterization of a cellular model. P R Health Sci J. 1998;17:327–333
  131. Martinez JA, Torres-Negron I, Amigo LA, Banerjee DK. Expression of Glc3Man9GlcNAc2-PP-Dol is a prerequisite for capillary endothelial cell proliferation. Cell Mol Biol. 1999;45:137–152
  132. Smith LE, Kopchick JJ, Chen W, Knapp J, Kinose F, Daley D. Essential role of growth hormone in ischemia- induced retinal neovascularization. Science. 1997;276:1706–1709
  133. Nakao-Hayashi J, Ito H, Kanayasu T, Morita I, Murota S. Stimulatory effects of insulin and insulin-like growth factor I on migration and tube formation by vascular endothelial cells. Atherosclerosis. 1992;92:141–149
  134. Steele VE, Holmes CA, Hawk ET, Kopelovich L, Lubet RA, Crowell JA. Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev. 1999;8:467–483
  135. Gati I, Bergstrom M, Csoka K, Muhr C, Carlsson J. Effects of the 5-lipoxygenase inhibitors AA-863 and U-60,257 on human glioma cell lines. Prostaglandins Leukot Essent Fatty Acids. 1990;40:117–124
  136. Anderson KM, Seed TM, Peng J, Jajeh A, Meng J, Harris JE. Morphologic changes of apoptosis induced in human chronic myelogenous leukemia “blast” cells by SC41661A (Searle), a selective inhibitor of 5- lipoxygenase. Scanning Microse. 1994;8:675–684
  137. Anderson KM, Seed T, Plate JM, Jajeh A, Meng J, Harris JE. Selective inhibitors of 5-lipoxygenase reduce CML blast cell proliferation and induce limited differentiation and apoptosis. Leuk Res. 1995;19:789–801
  138. Anderson KM, Seed T, Jajeh A, Dudeja P, Byun T, Meng J. An in vivo inhibitor of 5-lipoxygenase, MK886, at micromolar concentration induces apoptosis in U937 and CML cells. Anticancer Res. 1996;16:2589–2599
  139. Buyn T, Dudeja P, Harris JE, Ou D, Seed T, Sawlani D. A 5-lipoxygenase inhibitor at micromolar concentration raises intracellular calcium in U937 cells prior to their physiologic cell death. Prostaglandins Leukot Essent Fatty Acids. 1997;56:69–77
  140. Ogmundsdottir HM, Zoega GM, Gissurarson SR, Ingolfsdottir K. Anti-proliferative effects of lichen-derived inhibitors of 5- lipoxygenase on malignant cell-lines and mitogen-stimulated lymphocytes. J Pharm Pharmacol. 1998;50:107–115
  141. Anderson KM, Seed T, Vos M, Mulshine J, Meng J, Alrefai W. 5-Lipoxygenase inhibitors reduce PC-3 cell proliferation and initiate nonnecrotic cell death. Prostate. 1998;37:161–173
  142. Avis IM, Jett M, Boyle T, Vos MD, Moody T, Treston AM. Growth control of lung cancer by interruption of 5- lipoxygenase- mediated growth factor signaling. J Clin Invest. 1996;97:806–813
  143. Hussey HJ, Tisdale MJ. Inhibition of tumour growth by lipoxygenase inhibitors. Br J Cancer. 1996;74:683–687
  144. Ghosh J, Myers CE. Arachidonic acid stimulates prostate cancer cell growth: critical role of 5-lipoxygenase. Biochem Biophys Res Commun. 1997;235:418–423
  145. Ghosh J, Myers CE. Inhibition of arachidonate 5- lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Natl Acad Sci USA. 1998;95:13182–13187
  146. Ding XZ, Iversen P, Cluck MW, Knezetic JA, Adrian TE. Lipoxygenase inhibitors abolish proliferation of human pancreatic cancer cells. Biochem Biophys Res Commun. 1999;261:218–223
  147. Jiang H, Yamamoto S, Kato R. Inhibition of two-stage skin carcinogenesis as well as complete skin carcinogenesis by oral administration of TMK688, a potent lipoxygenase inhibitor. Carcinogenesis. 1994;15:807–812
  148. Rioux N, Castonguay A. Inhibitors of lipoxygenase: a new class of cancer chemopreventive agents. Carcinogenesis. 1998;19:1393–1400
  149. Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther. 1992;261:1143–1146
  150. Safayhi H, Sailer ER, Ammon HP. Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid. Mol Pharmacol. 1995;47:1212–1216
  151. Sailer ER, Schweizer S, Boden SE, Ammon HP, Safayhi H. Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling. Eur J Biochem. 1998;256:364–368
  152. Gupta I, Parihar A, Malhotra P, Singh GB, Ludtke R, Safayhi H. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res. 1997;2:37–43
  153. Gupta I, Gupta V, Parihar A, Gupta S, Ludtke R, Safayhi H. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo controlled, 6-week clinical study. Eur J Med Res. 1998;3:511–514
  154. Shao Y, Ho CT, Chin CK, Badmaev V, Ma W, Huang MT. Inhibitory activity of boswellic acids from Boswellia serrata against human leukemia HL-60 cells in culture. Planta Med. 1998;64:328–331
  155. Hoernlein RF, Orlikowsky T, Zehrer C, Niethammer D, Sailer ER, Simmet T. Acetyl-11-keto-beta-boswellic acid induces apoptosis in HL-60 and CCRF-CEM cells and inhibits topoisomerase I. J Pharmacol Exp Ther. 1999;288:613–619
  156. Jing Y, Nakajo S, Xia L, Nakaya K, Fang Q, Waxman S. Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines. Leuk Res. 1999;23:43–50
  157. Glaser T, Winter S, Groscurth P, Safayhi H, Sailer ER, Ammon HP. Boswellic acids and malignant glioma: induction of apoptosis but no modulation of drug sensitivity. Br J Cancer. 1999;80:756–765
  158. Winking M, Sarikaya S, Jodicke A. Boswellic acids inhibit glioma growth. J Cancer Res Clin Oncol. 1998;124:R141
  159. Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med. 1995;1:1046–1051
  160. Wick W, Grimmel C, Wagenknecht B, Dichgans J, Weller M. Betulinic acid-induced apoptosis in glioma cells: A sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J Pharmacol Exp Ther. 1999;289:1306–1312
  161. Fulda S, Jeremias I, Steiner HH, Pietsch T, Debatin KM. Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells. Int J Cancer. 1999;82:435–441
  162. Natarajan R, Nadler J. Role of lipoxygenases in breast cancer. Front Biosci. 1998;3:E81–E88
  163. Honn KV, Tang DG, Gao X, Butovich IA, Liu B, Timar J. 12-lipoxygenases and 12(S)-HETE: role in cancer metastasis. Cancer Metastasis Rev. 1994;13:365–396
  164. Gao X, Grignon DJ, Chbihi T, Zacharek A, Chen YQ, Sakr W. Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. Urology. 1995;46:227–237
  165. Liu XH, Connolly JM, Rose DP. Eicosanoids as mediators of linoleic acid-stimulated invasion and type IV collagenase production by a metastatic human breast cancer cell line. Clin Exp Metastasis. 1996;14:145–152
  166. Liu XH, Connolly JM, Rose DP. The 12-lipoxygenase gene-transfected MCF-7 human breast cancer cell line exhibits estrogen-independent, but estrogen and omega-6 fatty acid-stimulated proliferation in vitro, and enhanced growth in athymic nude mice. Cancer Lett. 1996;109:223–230
  167. Nie D, Hillman GG, Geddes T, Tang K, Pierson C, Grignon DJ. Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth. Cancer Res. 1998;58:4047–4051
  168. Dailey LA, Imming P. 12-Lipoxygenase: classification, possible therapeutic benefits from inhibition, and inhibitors. Curr Med Chem. 1999;6:389–398
  169. Connolly JM, Rose DP. Enhanced angiogenesis and growth of 12-lipoxygenase gene-transfected MCF-7 human breast cancer cells in athymic nude mice. Cancer Lett. 1998;132:107–112
  170. Chen YQ, Duniec ZM, Liu B, Hagmann W, Gao X, Shimoji K. Endogenous 12(S)-HETE production by tumor cells and its role in metastasis. Cancer Res. 1994;54:1574–1579
  171. Gao X, Porter AT, Honn KV. Involvement of the multiple tumor suppressor genes and 12-lipoxygenase in human prostate cancer. Therapeutic implications. Adv Exp Med Biol. 1997;407:41–53
  172. Liu B, Maher R, De Jonckheere JP, Popat RU, Stojakovic S, Hannun YA. 12(S)-HETE increases the motility of prostate tumor cells through selective activation of PKC alpha. Adv Exp Med Biol. 1997;400B:707–718
  173. Honn KV, Tang DG. Eicosanoid 12(S)-HETE upregulates endothelial cell alpha V beta 3 integrin expression and promotes tumor cell adhesion to vascular endothelium. Adv Exp Med Biol. 1997;400B:765–773
  174. Tang K, Honn KV. 12(S)-HETE in cancer metastasis. Adv Exp Med Biol. 1999;447:181–191
  175. Yano H, Mizoguchi A, Fukuda K, Haramaki M, Ogasawara S, Momosaki S. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res. 1994;54:448–454
  176. Motoo Y, Sawabu N. Antitumor effects of saikosaponins, baicalin and baicalein on human hepatoma cell lines. Cancer Lett. 1994;86:91–95
  177. Matsuzaki Y, Kurokawa N, Terai S, Matsumura Y, Kobayashi N, Okita K. Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res. 1996;87:170–177
  178. Inoue T, Jackson EK. Strong antiproliferative effects of baicalein in cultured rat hepatic stellate cells [In Process Citation]. Eur J Pharmacol. 1999;378:129–135
  179. Natarajan R, Gonzales N, Lanting L, Nadler J. Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy. Hypertension. 1994;23:1142–1147
  180. Wen Y, Nadler JL, Gonzales N, Scott S, Clauser E, Natarajan R. Mechanisms of ANG II-induced mitogenic responses: role of 12- lipoxygenase and biphasic MAP kinase. Am J Physiol. 1996;271:C1212–C1220
  181. Nishio E, Watanabe Y. Role of the lipoxygenase pathway in phenylephrine-induced vascular smooth muscle cell proliferation and migration. Eur J Pharmacol. 1997;336:267–273
  182. Nakahama K, Morita I, Murota S. Effects of endogenously produced arachidonic acid metabolites on rat mesangial cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1994;51:177–182
  183. Thun MJ. NSAID use and decreased risk of gastrointestinal cancers. Gastroenterol Clin North Am. 1996;25:333–348
  184. Sheng H, Shao J, Kirkland SC, Isakson P, Coffey RJ, Morrow J. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest. 1997;99:2254–2259
  185. Hara A, Yoshimi N, Niwa M, Ino N, Mori H. Apoptosis induced by NS-398, a selective cyclooxygenase-2 inhibitor, in human colorectal cancer cell lines. Jpn J Cancer Res. 1997;88:600–604
  186. Kawamori T, Rao CV, Seibert K, Reddy BS. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, against colon carcinogenesis. Cancer Res. 1998;58:409–412
  187. Watson AJ. Chemopreventive effects of NSAIDs against colorectal cancer: regulation of apoptosis and mitosis by COX-1 and COX-2. Histol Histopathol. 1998;13:591–597
  188. Taketo MM. COX-2 and colon cancer. Inflamm Res. 1998;47 Suppl 2:S112–S116
  189. Fukutake M, Nakatsugi S, Isoi T, Takahashi M, Ohta T, Mamiya S. Suppressive effects of nimesulide, a selective inhibitor of cyclooxygenase-2, on azoxymethane-induced colon carcinogenesis in mice. Carcinogenesis. 1998;19:1939–1942
  190. Ahnen DJ. Colon cancer prevention by NSAIDs: what is the mechanism of action?. Eur J Surg Suppl. 1998;111–114
  191. Fischer SM, Lo HH, Gordon GB, Seibert K, Kelloff G, Lubet RA. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog. 1999;25:231–240
  192. Gilhooly EM, Rose DP. The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines. Int J Oncol. 1999;15:267–270
  193. Hwang D, Scollard D, Byrne J, Levine E. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst. 1998;90:455–460
  194. Majima M, Isono M, Ikeda Y, Hayashi I, Hatanaka K, Harada Y. Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants. Jpn J Pharmacol. 1997;75:105–114
  195. Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer Res. 1999;59:4574–4577
  196. Yamada M, Kawai M, Kawai Y, Mashima Y. The effect of selective cyclooxygenase-2 inhibitor on corneal angiogenesis in the rat. Curr Eye Res. 1999;19:300–304
  197. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN. Cyclooxygenase regulates angiogenesis induced by colon cancer cells [published erratum appears in Cell 1998 Jul 24; 94(2): following 271]. Cell. 1998;93:705–716
  198. Karmali RA, Reichel P, Cohen LA, Terano T, Hirai A, Tamura Y. The effects of dietary omega-3 fatty acids on the DU-145 transplantable human prostatic tumor. Anticancer Res. 1987;7:1173–1179
  199. Rose DP, Cohen LA. Effects of dietary menhaden oil and retinyl acetate on the growth of DU 145 human prostatic adenocarcinoma cells transplanted into athymic nude mice. Carcinogenesis. 1988;9:603–605
  200. Gabor H, Blank EW, Ceriani RL. Effect of dietary fat and monoclonal antibody therapy on the growth of human mammary adenocarcinoma MX-1 grafted in athymic mice. Cancer Lett. 1990;52:173–178
  201. Sakaguchi M, Rowley S, Kane N, Imray C, Davies A, Jones C. Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids. Br J Cancer. 1990;62:742–747
  202. de Bravo MG, de Antueno RJ, Toledo J, De Tomas ME, Mercuri OF, Quintans C. Effects of an eicosapentaenoic and docosahexaenoic acid concentrate on a human lung carcinoma grown in nude mice. Lipids. 1991;26:866–870
  203. Welsch CW, Oakley CS, Chang CC, Welsch MA. Suppression of growth by dietary fish oil of human breast carcinomas maintained in three different strains of immune- deficient mice. Nutr Cancer. 1993;20:119–127
  204. Rose DP, Connolly JM, Rayburn J, Coleman M. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J Natl Cancer Inst. 1995;87:587–592
  205. Senzaki H, Iwamoto S, Ogura E, Kiyozuka Y, Arita S, Kurebayashi J. Dietary effects of fatty acids on growth and metastasis of KPL-1 human breast cancer cells in vivo and in vitro. Anticancer Res. 1998;18:1621–1627
  206. Maehle L, Lystad E, Eilertsen E, Einarsdottir E, Hostmark AT, Haugen A. Growth of human lung adenocarcinoma in nude mice is influenced by various types of dietary fat and vitamin E. Anticancer Res. 1999;19:1649–1655
  207. Calder PC, Davis J, Yaqoob P, Pala H, Thies F, Newsholme EA. Dietary fish oil suppresses human colon tumour growth in athymic mice. Clin Sci (Colch). 1998;94:303–311
  208. Rose DP, Connolly JM, Coleman M. Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice. Clin Cancer Res. 1996;2:1751–1756
  209. McCarty MF. Fish oil may impede tumour angiogenesis and invasiveness by down-regulating protein kinase C and modulating eicosanoid production. Med Hypotheses. 1996;46:107–115
  210. Kanayasu T, Morita I, Nakao-Hayashi J, Asuwa N, Fujisawa C, Ishii T. Eicosapentaenoic acid inhibits tube formation of vascular endothelial cells in vitro. Lipids. 1991;26:271–276
  211. Yang SP, Morita I, Murota SI. Eicosapentaenoic acid attenuates vascular endothelial growth factor-induced proliferation via inhibiting Flk-1 receptor expression in bovine carotid artery endothelial cells. J Cell Physiol. 1998;176:342–349
  212. Tisdale MJ, Dhesi JK. Inhibition of weight loss by omega-3 fatty acids in an experimental cachexia model. Cancer Res. 1990;50:5022–5026
  213. Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition. 1996;12:S27–S30
  214. Tisdale MJ. Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia. Nutrition. 1996;12:S31–S33
  215. Ohira T, Nishio K, Ohe Y, Arioka H, Nishio M, Funayama Y. Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation. J Cancer Res Clin Oncol. 1996;122:711–715
  216. Barber MD, Ross JA, Fearon KC. The anti-cachectic effect of fatty acids. Proc Nutr Soc. 1998;57:571–576
  217. Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer. 1999;81:80–86
  218. Caughey GE, Pouliot M, Cleland LG, James MJ. Regulation of tumor necrosis factor-alpha and IL-1 beta synthesis by thromboxane A2 in nonadherent human monocytes. J Immunol. 1997;158:351–358
  219. Altavilla D, Squadrito F, Canale P, Ioculano M, Squadrito G, Campo GM. G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, inhibits tumor necrosis factor-alpha biosynthesis. Eur J Pharmacol. 1995;286:31–39
  220. Kuhn DC, Stauffer JL, Gaydos LJ, Lacey SL, Demers LM. An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages. Prostaglandins. 1993;46:195–205
  221. Miller CC, McCreedy CA, Jones AD, Ziboh VA. Oxidative metabolism of dihomogammalinolenic acid by guinea pig epidermis: evidence of generation of anti-inflammatory products. Prostaglandins. 1988;35:917–938
  222. Miller CC, Tang W, Ziboh VA, Fletcher MP. Dietary supplementation with ethyl ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty acids induces epidermal generation of local putative anti-inflammatory metabolites. J Invest Dermatol. 1991;96:98–103
  223. Ziboh VA, Fletcher MP. Dose-response effects of dietary gamma-linolenic acid-enriched oils on human polymorphonuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin Nutr. 1992;55:39–45
  224. Horrobin DF, Ziboh VA. The importance of linoleic acid metabolites in cancer metastasis and in the synthesis and actions of 13-HODE. Adv Exp Med Biol. 1997;433:291–294
  225. Dippenaar N, Booyens J, Fabbri D, Engelbrecht P, Katzeff IE. The reversibility of cancer: evidence that malignancy in human hepatoma cells is gamma-linolenic acid deficiency-dependent. S Afr Med J. 1982;62:683–685
  226. Booyens J, Dippenaar N, Fabbri D, Engelbrecht P, Louwrens CC, Katzeff IE. Some effects of linoleic acid and gamma-linolenic acid on the proliferation of human hepatoma cells in culture. S Afr Med J. 1984;65:607–612
  227. Botha JH, Robinson KM, Leary WP. The response of human carcinoma cell lines to gamma-linolenic acid with special reference to the effects of agents which influence prostaglandin and thromboxane synthesis. Prostaglandins Leukot Med. 1985;19:63–77
  228. Fujiwara F, Todo S, Imashuku S. Antitumor effect of gamma-linolenic acid on cultured human neuroblastoma cells. Prostaglandins Leukot Med. 1986;23:311–320
  229. Cantrill RC, Ells GW, de Antueno RJ, Elliot M, Raha SK, Horrobin DF. The effect of n-6 fatty acids on normal and v-Ki ras transformed NIH- 3T3 cells. Anticancer Res. 1992;12:2197–2201
  230. Hrelia S, Bordoni A, Biagi P, Rossi CA, Bernardi L, Horrobin DF. gamma-Linolenic acid supplementation can affect cancer cell proliferation via modification of fatty acid composition. Biochem Biophys Res Commun. 1996;225:441–447
  231. Jiang WG, Bryce RP, Horrobin DF, Mansel RE. gamma- Linolenic acid blocks cell cycle progression by regulating phosphorylation of p27kip1 and p57kip2 and their interactions with other cycle regulators in cancer cells. Int J Oncol. 1998;13:611–617
  232. el-Ela SH, Prasse KW, Carroll R, Bunce OR. Effects of dietary primrose oil on mammary tumorigenesis induced by 7, 12- dimethylbenz(a)anthracene. Lipids. 1987;22:1041–1044
  233. Ramchurren N, Karmali R. Effects of gamma-linolenic and dihomo-gamma-linolenic acids on 7,12-dimethylbenz(alpha)anthracene-induced mammary tumors in rats. Prostaglandins Leukot Essent Fatty Acids. 1995;53:95–101
  234. de Bravo MG, Tournier H, Schinella G, Viaggi M, Quintans C. [Effect of dietary supplementation with gamma-linolenic acid on the growth of a human lung carcinoma implanted in nude mice]. Medicina (B Aires). 1995;55:670–674
  235. Das UN. Tumoricidal action of cis-unsaturated fatty acids and their relationship to free radicals and lipid peroxidation. Cancer Lett. 1991;56:235–243
  236. Takeda S, Sim PG, Horrobin DF, Sanford T, Chisholm KA, Simmons V. Mechanism of lipid peroxidation in cancer cells in response to gamma-linolenic acid (GLA) analyzed by GC-MS(I): Conjugated dienes with peroxyl (or hydroperoxyl) groups and cell-killing effects. Anticancer Res. 1993;13:193–199
  237. Cantrill RC, Ells G, Chisholm K, Horrobin DF. Concentration-dependent effect of iron on gamma-linolenic acid toxicity in ZR-75-1 human breast tumor cells in culture. Cancer Lett. 1993;72:99–102
  238. Zurier RB, Rossetti RG, Jacobson EW, DeMarco DM, Liu NY, Temming JE. gamma-Linolenic acid treatment of rheumatoid arthritis. A randomized, placebo-controlled trial. Arthritis Rheum. 1996;39:1808–1817
  239. Cai J, Jiang WG, Mansel RE. Inhibition of the expression of VE-cadherin/catenin complex by gamma linolenic acid in human vascular endothelial cells, and its impact on angiogenesis. Biochem Biophys Res Commun. 1999;258:113–118
  240. Cai J, Jiang WG, Mansel RE. Inhibition of angiogenic factor- and tumour-induced angiogenesis by gamma linolenic acid. Prostaglandins Leukot Essent Fatty Acids. 1999;60:21–29
  241. Stoner GD, Mukhtar H. Polyphenols as cancer chemopreventive agents. J Cell Biochem Suppl. 1995;22:169–180
  242. Katiyar SK, Mukhtar H. Tea antioxidants in cancer chemoprevention. J Cell Biochem Suppl. 1997;27:59–67
  243. Dreosti IE, Wargovich MJ, Yang CS. Inhibition of carcinogenesis by tea: the evidence from experimental studies. Crit Rev Food Sci Nutr. 1997;37:761–770
  244. Imai K, Suga K, Nakachi K. Cancer-preventive effects of drinking green tea among a Japanese population. Prev Med. 1997;26:769–775
  245. Paschka AG, Butler R, Young CY. Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate. Cancer Lett. 1998;130:1–7
  246. Wang ZY, Huang MT, Ho CT, Chang R, Ma W, Ferraro T. Inhibitory effect of green tea on the growth of established skin papillomas in mice. Cancer Res. 1992;52:6657–6665
  247. Liao S, Umekita Y, Guo J, Kokontis JM, Hiipakka RA. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett. 1995;96:239–243
  248. Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett. 1998;133:19–26
  249. Conney AH, Lu Y, Lou Y, Xie J, Huang M. Inhibitory effect of green and black tea on tumor growth. Proc Soc Exp Biol Med. 1999;220:229–233
  250. Okabe S, Ochiai Y, Aida M, Park K, Kim SJ, Nomura T. Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines. Jpn J Cancer Res. 1999;90:733–739
  251. Valcic S, Timmermann BN, Alberts DS, Wachter GA, Krutzsch M, Wymer J. Inhibitory effect of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 1996;7:461–468
  252. Hibasami H, Komiya T, Achiwa Y, Ohnishi K, Kojima T, Nakanishi K. Induction of apoptosis in human stomach cancer cells by green tea catechins. Oncol Rep. 1998;5:527–529
  253. Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998;19:611–616
  254. Chen ZP, Schell JB, Ho CT, Chen KY. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett. 1998;129:173–179
  255. Okabe S, Ochiai Y, Aida M, Park K, Kim SJ, Nomura T. Mechanistic aspects of green tea as a cancer preventive: effect of components on human stomach cancer cell lines. Jpn J Cancer Res. 1999;90:733–739
  256. Otsuka T, Ogo T, Eto T, Asano Y, Suganuma M, Niho Y. Growth inhibition of leukemic cells by (-)-epigallocatechin gallate, the main constituent of green tea. Life Sci. 1998;63:1397–1403
  257. Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998;89:254–261
  258. Cao Y, Cao R. Angiogenesis inhibited by drinking tea [letter]. Nature. 1999;398:381
  259. McCarty MF. Polyphenol-mediated inhibition of AP-1 transactivating activity may slow cancer growth by impeding angiogenesis and tumor invasiveness. Med Hypotheses. 1998;50:511–514
  260. Yoshioka K, Deng T, Cavigelli M, Karin M. Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. Proc Natl Acad Sci USA. 1995;92:4972–4976
  261. Barthelman M, Bair WB, Stickland KK, Chen W, Timmermann BN, Valcic S. (-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis. 1998;19:2201–2204
  262. Chung JY, Huang C, Meng X, Dong Z, Yang CS. Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: structure-activity relationship and mechanisms involved [In Process Citation]. Cancer Res. 1999;59:4610–4617
  263. Dong Z, Ma W, Huang C, Yang CS. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins. Cancer Res. 1997;57:4414–4419
  264. Dong Z, Birrer MJ, Watts RG, Matrisian LM, Colburn NH. Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. Proc Natl Acad Sci USA. 1994;91:609–613
  265. Lavrovsky V, Dong Z, Ma WY, Colburn N. Drug-induced reversion of progression phenotype is accompanied by reversion of AP-1 phenotype in JB6 cells. In Vitro Cell Dev Biol Anim. 1996;32:234–237
  266. Huang C, Ma WY, Dawson MI, Rincon M, Flavell RA, Dong Z. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci USA. 1997;94:5826–5830
  267. Young MR, Li JJ, Rincon M, Flavell RA, Sathyanarayana BK, Hunziker R. Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion. Proc Natl Acad Sci USA. 1999;96:9827–9832
  268. Karin M, Liu Z, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol. 1997;9:240–246
  269. Lin CW, Georgescu HI, Evans CH. The role of AP-1 in matrix metalloproteinase gene expression. Agents Actions. 1993;39:C215–C218
  270. Benbow U, Brinckerhoff CE. The AP-1 site and MMP gene regulation: what is all the fuss about?. Matrix Biol. 1997;15:519–526
  271. Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999;13:781–792
  272. Appelt LC, Reicks MM. Soy feeding induces phase II enzymes in rat tissues. Nutr Cancer. 1997;28:270–275
  273. Wang W, Liu LQ, Higuchi CM, Chen H. Induction of NADPH: quinone reductase by dietary phytoestrogens in colonic Colo205 cells. Biochem Pharmacol. 1998;56:189–195
  274. Zhou JR, Mukherjee P, Gugger ET, Tanaka T, Blackburn GL, Clinton SK. Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis, and angiogenesis. Cancer Res. 1998;58:5231–5238
  275. Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr. 1999;129:1628–1635
  276. Ha YL, Storkson J, Pariza MW. Inhibition of benzo(a) pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res. 1990;50:1097–1101
  277. Ip C, Chin SF, Scimeca JA, Pariza MW. Mammary cancer prevention by conjugated dienoic derivative of linoleic acid. Cancer Res. 1991;51:6118–6124
  278. Ip C, Scimeca JA, Thompson HJ. Conjugated linoleic acid. A powerful anticarcinogen from animal fat sources. Cancer. 1994;74:1050–1054
  279. Belury MA. Conjugated dienoic linoleate: a polyunsaturated fatty acid with unique chemoprotective properties. Nutr Rev. 1995;53:83–89
  280. Ip C, Briggs SP, Haegele AD, Thompson HJ, Storkson J, Scimeca JA. The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level or type of fat in the diet. Carcinogenesis. 1996;17:1045–1050
  281. Visonneau S, Cesano A, Tepper SA, Scimeca JA, Santoli D, Kritchevsky D. Conjugated linoleic acid suppresses the growth of human breast adenocarcinoma cells in SCID mice. Anticancer Res. 1997;17:969–973
  282. Cesano A, Visonneau S, Scimeca JA, Kritchevsky D, Santoli D. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res. 1998;18:1429–1434
  283. Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY, Portocarrero CP, Peck LW, Nickel KP. Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat [published erratum appears in Biochem Biophys Res Commun 1998 Jun 29; 247(3): 911]. Biochem Biophys Res Commun. 1998;244:678–682
  284. Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB. Differentiation and reversal of malignant changes in colon cancer through PPARgamma [see comments]. Nat Med. 1998;4:1046–1052
  285. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci USA. 1999;96:3951–3956
  286. Takahashi N, Okumura T, Motomura W, Fujimoto Y, Kawabata I, Kohgo Y. Activation of PPARgamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett. 1999;455:135–139
  287. Sugimura A, Kiriyama Y, Nochi H, Tsuchiya H, Tamoto K, Sakurada Y. Troglitazone suppresses cell growth of myeloid leukemia cell lines by induction of p21WAF1/CIP1 cyclin-dependent kinase inhibitor. Biochem Biophys Res Commun. 1999;261:833–837
  288. Keelan JA, Sato TA, Marvin KW, Lander J, Gilmour RS, Mitchell MD. 15-Deoxy-Delta(12,14)-prostaglandin J(2), a ligand for peroxisome proliferator-activated receptor-gamma, induces apoptosis in JEG3 choriocarcinoma cells. Biochem Biophys Res Commun. 1999;262:579–585
  289. Clay CE, Namen AM, Atsumi G, Willingham MC, High KP, Kute TE. Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis. 1999;20:1905–1911
  290. Banni S, Angioni E, Casu V, Melis MP, Carta G, Corongiu FP. Decrease in linoleic acid metabolites as a potential mechanism in cancer risk reduction by conjugated linoleic acid. Carcinogenesis. 1999;20:1019–1024
  291. Schrauzer GN. Selenium and cancer: a review. Bioinorg Chem. 1976;5:275–281
  292. Schrauzer GN, White DA, Schneider CJ. Selenium and cancer: effects of selenium and of the diet on the genesis of spontaneous mammary tumors in virgin inbred female C3H/St mice. Bioinorg Chem. 1978;8:387–396
  293. Griffin AC. Role of selenium in the chemoprevention of cancer. Adv Cancer Res. 1979;29:419–442
  294. Combs GFJ, Clark LC. Can dietary selenium modify cancer risk?. Nutr Rev. 1985;43:325–331
  295. Ip C. Selenium inhibition of chemical carcinogenesis. Fed Proc. 1985;44:2573–2578
  296. Ip C. The chemopreventive role of selenium in carcinogenesis. Adv Exp Med Biol. 1986;206:431–447
  297. Ip C, Ganther HE. Activity of methylated forms of selenium in cancer prevention. Cancer Res. 1990;50:1206–1211
  298. Ip C, Hayes C, Budnick RM, Ganther HE. Chemical form of selenium, critical metabolites, and cancer prevention. Cancer Res. 1991;51:595–600
  299. Clark LC. The epidemiology of selenium and cancer. Fed Proc. 1985;44:2584–2589
  300. Clark LC, Cantor KP, Allaway WH. Selenium in forage crops and cancer mortality in U.S.counties. Arch Environ Health. 1991;46:37–42
  301. Clark LC, Combs GFJ, Turnbull BW, Slate EH, Chalker DK, Chow J. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group [see comments] [published erratum appears in JAMA 1997 May 21; 277(19): 1520]. JAMA. 1996;276:1957–1963
  302. Clark LC, Dalkin B, Krongrad A, Combs GFJ, Turnbull BW, Slate EH. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol. 1998;81:730–734
  303. Ip C, Lisk DJ, Thompson HJ. Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis. Carcinogenesis. 1996;17:1979–1982
  304. Prontera C, Mariani B, Rossi C, Poggi A, Rotilio D. Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma. Int J Cancer. 1999;81:761–766
  305. Volpert OV, Ward WF, Lingen MW, Chesler L, Solt DB, Johnson MD. Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats [see comments]. J Clin Invest. 1996;98:671–679
  306. Vogt B, Frey FJ. Inhibition of angiogenesis in Kaposi’s sarcoma by captopril [letter]. Lancet. 1997;349:1148
  307. Bouck N, Campbell S. Anti-cancer dividends from captopril and other inhibitors of angiogenesis [editorial]. J Nephrol. 1998;11:3–4
  308. Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, MacKinnon PL. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? [see comments]. Lancet. 1998;352:179–184
  309. D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 1994;91:4082–4085
  310. Kruse FE, Joussen AM, Rohrschneider K, Becker MD, Volcker HE. Thalidomide inhibits corneal angiogenesis induced by vascular endothelial growth factor. Graefes Arch Clin Exp Ophthalmol. 1998;236:461–466
  311. Neubert R, Hinz N, Thiel R, Neubert D. Down-regulation of adhesion receptors on cells of primate embryos as a probable mechanism of the teratogenic action of thalidomide. Life Sci. 1996;58:295–316
  312. Nogueira AC, Neubert R, Felies A, Jacob-Muller U, Frankus E, Neubert D. Thalidomide derivatives and the immune system. 6. Effects of two derivatives with no obvious teratogenic potency on the pattern of integrins and other surface receptors on blood cells of marmosets. Life Sci. 1996;58:337–348
  313. McCarty MF. Thalidomide may impede cell migration in primates by down-regulating integrin beta-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis. Med Hypotheses. 1997;49:123–131
  314. Bauer KS, Dixon SC, Figg WD. Inhibition of angiogenesis by thalidomide requires metabolic activation, which is species-dependent. Biochem Pharmacol. 1998;55:1827–1834
  315. Rose ML, Madren J, Bunzendahl H, Thurman RG. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999;20:793–798
  316. Prestera T, Talalay P. Electrophile and antioxidant regulation of enzymes that detoxify carcinogens. Proc Natl Acad Sci USA. 1995;92:8965–8969
  317. Zhang Y, Talalay P. Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res. 1994;54:1976s–1981s
  318. Talalay P, Fahey JW, Holtzclaw WD, Prestera T, Zhang Y. Chemoprotection against cancer by phase 2 enzyme induction. Toxicol Lett. 1995;82–83:173–179
  319. Barcelo S, Gardiner JM, Gescher A, Chipman JK. CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane [see comments]. Carcinogenesis. 1996;17:277–282
  320. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci USA. 1997;94:10367–10372
  321. Mello FA, Meneghini R. In vivo formation of single-strand breaks in DNA by hydrogen peroxide is mediated by the Haber-Weiss reaction. Biochim Biophys Acta. 1984;781:56–63
  322. Mello-Filho AC, Meneghini R. Iron is the intracellular metal involved in the production of DNA damage by oxygen radicals. Mutat Res. 1991;251:109–113
  323. Nascimento AL, Meneghini R. Cells transfected with transferrin receptor cDNA lacking the iron regulatory domain become more sensitive to the DNA-damaging action of oxidative stress. Carcinogenesis. 1995;16:1335–1338
  324. Stevens RG. Iron and the risk of cancer. Med Oncol Tumor Pharmacother. 1990;7:177–181
  325. Reizenstein P. Iron, free radicals and cancer. Med Oncol Tumor Pharmacother. 1991;8:229–233
  326. Knekt P, Reunanen A, Takkunen H, Aromaa A, Heliovaara M, Hakulinen T. Body iron stores and risk of cancer. Int J Cancer. 1994;56:379–382
  327. Shaw NS, Chin CJ, Pan WH. A vegetarian diet rich in soybean products compromises iron status in young students. J Nutr. 1995;125:212–219
  328. Ball MJ, Bartlett MA. Dietary intake and iron status of Australian vegetarian women. Am J Clin Nutr. 1999;70:353–358
  329. Hann HW, Stahlhut MW, Blumberg BS. Iron nutrition and tumor growth: decreased tumor growth in iron- deficient mice. Cancer Res. 1988;48:4168–4170
  330. Weinberg ED. The role of iron in cancer. Eur J Cancer Prev. 1996;5:19–36

PII: S0306-9877(00)91126-5

doi: 10.1054/mehy.2000.1126

Medical Hypotheses
Volume 56, Issue 2 , Pages 137-154 , February 2001