Natural antimutagenic agents may prolong efficacy of human immunodeficiency virus drug therapy
Medical Hypotheses (United Kingdom), 1997, 48/3 (215-220)
The long-term efficacy of new combination drug therapies for human immunodeficiency virus infection may be limited by the tendency of transfected human immunodeficiency virus to mutate to drug-resistant forms. This argues for the use of safe antimutagenic measures as adjuvants to such therapies. Certain nutrients and food factors notably selenium, green-tea polyphenols, and cruciferous phytochemicals - can suppress cancer initiation and mutagenesis in animal and cell culture models; epidemiological studies suggest that ambient variations in consumption of these food factors can have an important impact on human cancer rates. Low-fat diets may reduce deoxyribonucleic acid base damage in human leukocytates. Thus, ample but safe intakes of selenium, green-tea polyphenols, and cruciferous vegetables, in the context of a diet low in fat and assimilable iron, can be expected to prolong the efficacy of drug therapy in subjects infected with the human immunodeficiency virus. These measures can also be recommended for cancer prevention in the general population.
Changes in levels of urinary estrogen metabolites after oral indole-3- carbinol treatment in humans
Journal of the National Cancer Institute (United Kingdom),1997, 89/10 (718-723)
Background: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). Purpose: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. Methods: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry. Results: In both men and women, 13C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha-hydroxyestrone, were lower after I3C treatment. Conclusions: These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. Implications: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.
Selective responsiveness of human breast cancer cells to indole-3-carbinol, a chemopreventive agent
J Natl Cancer Inst (UNITED STATES) Jan 19 1994
BACKGROUND: Indole-3-carbinol (I3C), a compound found in cabbage, broccoli, and brussels sprouts, inhibits the growth of mammary tumors when fed to certain strains of mice. The chemopreventive and antitumor effects of I3C depend on the species and tissue type. The mechanism of action and specific human cell types that respond to I3C are not known. PURPOSE: Our purpose was to study the mechanism of action of I3C in estrogen-responsive (MCF-7) and estrogen-nonresponsive (MDA-MB-231) human breast cancer cell lines. METHODS: Estrogen responsiveness was determined by the ability of estradiol to stimulate the growth of breast cancer cells deprived of estrogen. The effect of I3C was measured on cell growth, estradiol metabolism, and level of cytochrome P-4501A1. Growth was measured by cell counts and soft-agar assay, estrogen metabolism was examined by a radiometric assay, and the level of cytochrome P-4501A1 was measured by Western blots with a polyclonal antibody. RESULTS: I3C inhibits the growth of estrogen-responsive cell line MCF-7 but has little effect on estrogen-nonresponsive cell line MDA-MB-231. Specific C-2 hydroxylation of estrogen and induction of cytochrome P-4501A1 was enhanced by I3C in the MCF-7 but not in the MDA-MB-231 cells. CONCLUSION: I3C has specific antigrowth effects in human breast cancer cells. The inhibitory effects of I3C may involve selective induction of estradiol metabolism and the related cytochrome P-450 system that may be limited to estrogen-sensitive cells.