EFFECT OF AN AQUEOUS EXTRACT OF SELENIUM-ENRICHED GARLIC ON IN-VITRO MARKERS AND IN-VIVO EFFICACY IN CANCER PREVENTION

Previous work has shown that the efficacy of cancer prevention by sele nium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium, An aqueous extract containing 43 mu g Se/ml was prepared from lyophilized Se-garlic powder by the Soxhlet method, The activity of this Se-garlic extract was evaluated in a transformed mammary epith elial cell culture model for its effect on cell morphology, cell growt h, cell cycle progression and the induction of single and double stran ded breaks in DNA, Comparisons were also made with a similarly prepare d extract from regular garlic, Se-methylselenocysteine (a major water- soluble seleno-amino acid identified in Se-garlic) and selenite (used for fertilizing Se-garlic), In contrast to the regular garlic extract which produced little or no modulation of the above parameters, treatm ent with the Se-garlic extract resulted in growth inhibition, G(1) pha se cell cycle arrest and apoptotic DNA double strand breaks in the abs ence of DNA single strand breaks, This pattern of cellular responses w as duplicated with exposure to Se-methylselenocysteine. Selenite, on t he other hand, induced cell cycle blockage in the S/G(2)-M phase, and a marked increase in DNA single strand breaks (a measure of genotoxici ty) in addition to growth suppression, The chemopreventive efficacy of the two garlic extracts was also investigated in the rat methylnitros ourea mammary tumor model, Both extracts were supplemented in the diet for 1 month immediately following carcinogen administration, Signific ant cancer protection was observed with treatment by the Se-garlic ext ract (at 3 p.p.m. Se in the diet), while little benefit was noted with treatment by the regular garlic extract, Based on the above in vitro and in vivo findings, it is hypothesized that the Se-garlic extract, i n part via the action of Se-methylselenocysteine, is able to inhibit t umorigenesis by suppressing the proliferation and reducing the surviva l of the early transformed cells, Furthermore, the data also support t he concept that the modulation of certain in vitro markers may be of v alue in predicting the effectiveness of novel forms of selenium for ca ncer prevention.