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LE Magazine January 2004

New Promise for Cancer Prevention and Treatment

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
Despite some setbacks and negative findings, the trend in nutrition and cancer research is overwhelmingly positive. The Bethesda conference demonstrated that research is moving beyond the idea that eating fruits and vegetables helps prevent cancer, to identifying which compounds in plant food are cancer-preventing agents. Research is now focusing on how —not whether—phyto-compounds inhibit cancer cell growth.

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.

References

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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.

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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.

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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.

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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.

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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.

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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.

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