New Promise for Cancer Prevention and TreatmentJanuary 2004
The new research shows that I3C and its breakdown product DIM work synergistically to stop the growth of breast cancer cells, with I3C inhibiting a cancer-related gene (the gene for Cdk-6 kinase) that DIM does not. DIM and I3C both kill breast cancer cells.21 But maximum cell-killing effect occurs when both compounds are present. While I3C and DIM each have unique effects on genes that control the multiplication of cancer cells, they share some effects in common that have been dubbed “overlapping effects.” Life Extension advises its members to take I3C rather than DIM, as I3C naturally breaks down into DIM and other products that may have unknown beneficial effects. Taking DIM offers the benefits of only the one compound.
I3C stops breast cancer cells from multiplying through a unique, partly unknown pathway. Its effects against various types of breast cancer are so promising that the University of California researchers state: “In the case of estrogen-nonresponsive MDA-MB-231 cells, indole treatment (I3C) inhibited proliferation under conditions in which the antiestrogen tamoxifen had no effect, which suggests that a wider range of breast cancer cells responds to indoles than estrogen antagonists.” Their research adds to the growing evidence that I3C may form the basis of a powerful new therapy for breast cancer treatment. Its efficacy in prevention already has been established.22-25
Italian researchers recently created an artificial product from natural I3C that has twice the strength in estrogen-receptor-negative breast cancer cells.26 It inhibits the same critical enzyme (Cdk6 kinase) as I3C, but instead of activating the p21 tumor suppressor gene, it activates another known as p27. The researchers intend to pursue the “tetramer” they created as a drug. Preliminary evidence shows that it does not harm normal cells.
Cancer Research Continues to Advance
Nutrition and cancer researchers who attended the conference are more and more investigating the interactions of cancer-preventing compounds and proposing sophisticated new research to bring all the new findings together. They contend that a new kind of scientific review is needed to evaluate the potential of anti-cancer modalities to work together synergistically, with geneticists and nutritionists working in tandem. They note that cancer survivors need to be utilized as valuable sentinels of cancer prevention, and that the notion that a nutrient may be more effective at one stage of cancer than at another should be considered.
Researchers hope that these and other new developments—such as the use of sophisticated new computer models and imaging systems—will bring them that much closer to finally winning the war on cancer.
1. Veierod MB, Veierod MB, Laake P, Thelle DS. Dietary fat intake and risk of prostate cancer: a prospective study of 25,708 Norwegian men. Int J Cancer. 1997 Nov 27;73(5):634-8.
2. Giovannucci E, Rimm EB, Colditz GA, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst. 1993 Oct 6;85(19):1571-9.
3. Chan JM, Stampfer MJ, Ma J, Gann PH, Gaziano JM, Giovannucci EL. Dairy prod- ucts, calcium, and prostate cancer risk in the Physicians’ Health Study. Am J Clin Nutr. 2001 Oct;74(4):549-54.
4. Le Guevel R, Pakdel F. Assessment of oestrogenic potency of chemicals used as growth promoter by in-vitro methods. Hum Reprod. 2001 May;16(5):1030-6.
5. Yu H, Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000 Sep 20;92(18):1472-89.
6. Zhao H, Grossman HB, Spitz MR, Lerner SP, Zhang K, Wu X. Plasma levels of insulin- like growth factor-1 and binding protein-3, and their association with bladder cancer risk. J Urol. 2003 Feb;169(2):714-7.
7. Schoonmaker JP, Loerch SC, Fluharty FL, et al. Effect of an accelerated finishing program on performance, carcass characteristics, and circulating insulin-like growth factor 1 con- centration of early-weaned bulls and steers. J Anim Sci. 2002 Apr;80(4):900-10.
8. Lee CY, Lee HP, Jeong JH, et al. Effects of restricted feeding, low-energy diet, and implantation of trenbolone acetate plus estradiol on growth, carcass traits, and circu- lating concentrations of insulin-like growth factor (IGF)-1 and IGF-binding protein-3 in finishing barrows. J Anim Sci. 2002 Jan;80(1):84-93.
9. Adhami VM, Ahmad N, Mukhtar H. Molecular targets for green tea in prostate cancer prevention. J Nutr. 2003 Jul;133(7 Suppl):2417S-2424S.
10. Reyes N, et al. 2000. Microarray analysis of diet-induced alterations in gene expression in the ACI rat prostate. Eur J Cancer Prev 2002 Aug;11 Suppl 2: S37-42.
11. Danzin C, Jung MJ, Grove J, Bey P. Effect of a-difluoromethylornithine, an enzyme-acti- vated irreversible inhibitor of ornithine decarboxylase on polyamine levels in rat tis- sues. Life Sci. 1979 Feb 5;24(6):519-24.
12. Stewart JR, Artime MC, O’Brian CA. Resveratrol: a candidate nutritional sub- stance for prostate cancer prevention. J Nutr. 2003 Jul;133(7 Suppl):2440S-2443S.
13. Mitchell SH, Zhu W, Young CY. Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res. 1999 Dec 1;59(23):5892-5.
14. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan 10;275(5297):218-20.
15. Auborn KJ, Fan S, Rosen EM, et al. Indole- 3-carbinol is a negative regulator of estrogen. J Nutr. 2003 Jul;133(7 Suppl):2470S-2475S.
16. van Poppel G, Verhoeven DT, Verhagen H, Goldbohm RA. Brassica vegetables and can- cer prevention. Epidemiology and mecha- nisms. Adv Exp Med Biol. 1999;472:159-68.
17. Fowke JH, Chung FL, Jin F, et al. Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res. 2003 Jul 15;63(14):3980-6.
18. Kristal AR, Lampe JW. Brassica vegetables and prostate cancer risk: a review of the epi- demiological evidence. Nutr Cancer. 2002;42(1):1-9.
19. Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000 Jan 5;92(1):61-8.
20. Firestone GL, Bjeldanes LF. Indole-3- carbinol and 3-3’-diindolylmethane antiproliferative signaling pathways control cellcycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions. J Nutr. 2003 Jul;133(7 Suppl):2448S-2455S.
21. Hong C, Kim HA, Firestone GL, Bjeldanes LF. Diindolylmethane (DIM) induces a G1 cell cycle arrest in human breast cancer cells that is accompanied by Sp-1-mediated activation of p21WAF1CIP1 expression. Carcinogenesis. 2002 Aug;23(8):1297-305.
22. Michnovicz JJ, Bradlow HL. Altered estro- gen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer. 1991;16(1):59-66.
23. Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3- carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991 Sep;12(9):1571-4.
24. Jellinck PH, Newcombe AM, Forkert PG, Martucci CP. Distinct forms of hepatic androgen 6 beta-hydroxylase induced in the rat by indole-3-carbinol and pregnenolone carbonitrile. J Steroid Biochem Mol Biol. 1994 Nov;51(3-4):219-25.
25. Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995 May- Jun;15(3):709-16.
26. Brandi G, Paiardini M, Cervasi B, et al. A new indole-3-carbinol tetrameric derivative inhibits cyclin-dependent kinase 6 expression, and induces G1 cell cycle arrest in both estrogen-dependent and estrogen-indepen- dent breast cancer cell lines. Cancer Res. 2003 Jul 15;63(14):4028-36.