ANTIPROLIFERATIVE EFFECTS OF GARLIC AND ...

ANTIPROLIFERATIVE EFFECTS OF GARLIC AND ITS POTENTIAL CHEMOPREVENTIVE ACTIVITY. JT Pinto*, BF. Krasnikov, AJL. Cooper. Burke Med Res Inst, White Plains, NY.10605. Krasnikov, AJL. Cooper. Burke Med Res Inst, White Plains, NY.10605. Molecular investigations support an existing body of clinical and epidemiological data that garlic-derived allylsulfides have effects in reducing the risk of cancer. However, the precise mechanisms responsible for prevention of cancer remain to be elucidated. To understand possible biochemical mechanisms contributing to the protective effects of allylsulfides, the ability of these compounds to undergo various enzyme-catalyzed transformations was investigated. In addition to catalyzing γ-elimination reactions, γcystathionase can perform β-elimination reactions with cysteinyl S-conjugates derived from fresh and commercial garlic extracts, when the S-alkyl group (R) is larger than ethyl. The reaction products are pyruvate, ammonium and a sulfur-containing fragment (RSH). Substrates of γ-cystathionase from garlic include: S-allyl-L-cysteine (R = CH2=CHCH2-), S-allylmercapto-L-cysteine (R = CH2=CHCH2S-), Spropylmercapto-L-cysteine (R=CH3CH2CH2S-). Mercapto derivatives yield persulfide products (RSSH) that are potential sources of sulfane sulfur, which may modify protein function by reacting at important cysteinyl domains. Thus, β-elimination reactions with cysteine S-conjugates in garlic may modify growth of cancer cells by targeting redox-sensitive signal proteins at sulfhydryl sites, thereby regulating proliferation and/or apoptotic responses. Supported in part by AG14930 (AJLC), CNRU Grant CA 29502, and CA89815 (JTP) 93. Pinto JT, Krasnikov BF, and Cooper AL. Antiproliferative effects of garlic and its potential chemopreventive activity. Symposium: Significance of Garlic and its Constituents in Cancer and Cardiovascular Disease. Georgtown University, Washington, D.C. April 9-11, 2005