Previous work has shown that the efficacy of
cancer prevention by
selenium-enriched garlic (Se-garlic) is primarily dependent on the action of
selenium. An aqueous extract containing 43 micro 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 epithelial cell culture model for its effect on cell morphology, cell growth, cell cycle progression and the induction of single and double stranded breaks in
DNA. Comparisons were also made with a similarly prepared 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, treatment with the Se-garlic extract resulted in growth inhibition, GI phase cell cycle arrest and apoptotic
DNA double strand breaks in the absence of
DNA single strand breaks. This pattern of cellular responses was duplicated with exposure to
Se-methylselenocysteine.
Selenite, on the other hand, induced cell cycle blockage in the S/G2-M phase, and a marked increase in
DNA single strand breaks (a measure of genotoxicity) in addition to growth suppression. The chemopreventive efficacy of the two garlic extracts was also investigated in the rat
methylnitrosourea mammary
tumor model. Both extracts were supplemented in the diet for 1 month immediately following
carcinogen administration. Significant
cancer protection was observed with treatment by the Se-garlic extract (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, in part via the action of
Se-methylselenocysteine, is able to inhibit
tumorigenesis by suppressing the proliferation and reducing the survival of the early transformed cells. Furthermore, the data also support the concept that the modulation of certain in vitro markers may be of value in predicting the effectiveness of novel forms of
selenium for
cancer prevention.