Effect of an aqueous extract of selenium-enriched garlic on in vitro markers and in vivo efficacy in cancer prevention

Abstract

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.

Apoptosis and Angiogenesis in Cancer Prevention by Selenium

“…The genotoxicity (or lack of) effect of the two Se pools was based on studies with mammary cancer epithelial cells and leukemia cells (ref. 15,16,[23][24][25]. Abbreviations: Se-cys, selenocysteine; Se-Met, selenomethionine; CH,SeCN, methylselenocyanate; CH,SeCys, Se-methylselenocysteine; CH,Se02H, methylseleninic acid.…”

Protective effect of sodium selenite on genotoxicity to human whole blood cultures induced by aflatoxin B1

“…Selenium has been shown in animal studies to inhibit aflatoxin hepatocarcinogenesis . These inhibitory effects are supported by many diverse mechanisms, including inhibition of carcinogen formation, modulation of carcinogen metabolism, inhibition of mutagenesis and genotoxicity, inhibition of cell proliferation (Lu et al, 1996). It is important to verify lack of toxicity of selenium on different systems and to investigate mechanisms of its action throughout the whole processes of mutagenesis.…”

Chemopreventive Effect of Selenium-Enriched Japanese Radish Sprout against Breast Cancer Induced by 7,12-Dimethylbenz[a]anthracene in Rats

“…Of the many Se compounds involved in plants, MeSeCys is thought to be one of the most outstanding for its chemoprevention of chemical carcinogen-induced mammary cancer in rat model Lu et al 1996). The major Se form in the Se-enriched sprout used in this study was MeSeCys (80%), which clearly inhibited the Fig.…”

“…When the major chemical form of γ -glutamyl-Se-methylselenocysteine (73%), namely, Seenriched garlic, was added to the diet (3 ppm as Se), the incidence of tumors treated either by DMBA or MNU decreased from 83% -93% to 33% -47% Lu et al 1996). Moreover, when Se-enriched broccoli, a major chemical form (45%) of MeSeCys, was added (as final 3 ppm), the tumor incidence fell from 90% to 37% .…”