Antiproliferative effects of S-allylmercaptocysteine on colon cancer cellswhen tested alone or in combination with sulindac sulfide

Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Expe rimental carcinogenesis studies in animal models and in cell culture system s indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and pro motion phases of carcinogenesis, To provide a better understanding of the e ffects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allyl merraptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29, For com parison, we included the compound sulindac sulfide (SS), because sulindac c ompounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAG, inhibited the growth of both cell lines at doses s imilar to that of SS, SAMC also induced apoptosis, and this was associated with an increase in caspase-3-like activity. These affects of SAMC were acc ompanied by induction of jun kinase activity and a marked increase in endog enous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G(1) to S, SAMC inhibited progression at G(2)-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mit osis, Coadministration of SS with SAMC enhanced the growth inhibitory and a poptotic effects of SS. These findings suggest that SAMC may be useful in c olon cancer prevention when used alone or in combination with SS or other c hemopreventive agents.