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Experimental Therapeutics |
Herbert Irving Comprehensive Cancer Center [H. S., Y.K., J-W. S., I. B. W.] and Department of Pathology [V. M.], College of Physicians and Surgeons, Columbia University, New York, New York 10032; Department of Medicine, St. Luke’s-Roosevelt Hospital Center, New York, New York 10025 [H. S., S. F. M., P. R. H.]; Nutrition Research Laboratory and the Clinical Nutrition Research Unit [J. T. P., R. S. R.] and Flow Cytometry Core Facility [T. D.], Memorial Sloan Kettering Cancer Center, New York, New York 10021
Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of carcinogenesis. To provide a better understanding of the effects of allium derivatives on the prevention of colon cancer, we examined two water-soluble derivatives of garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), for their effects on proliferation and cell cycle progression in two human colon cancer cell lines, SW-480 and HT-29. For comparison, we included the compound sulindac sulfide (SS), because sulindac compounds are well-established colon cancer chemopreventive agents. We found that SAMC, but not SAC, inhibited the growth of both cell lines at doses similar to that of SS. SAMC also induced apoptosis, and this was associated with an increase in caspase3-like activity. These affects of SAMC were accompanied by induction of jun kinase activity and a marked increase in endogenous levels of reduced glutathione. Although SS caused inhibition of cell cycle progression from G1 to S, SAMC inhibited progression at G2-M, and a fraction of the SW-480 and HT-29 cells were specifically arrested in mitosis. Coadministration of SS with SAMC enhanced the growth inhibitory and apoptotic effects of SS. These findings suggest that SAMC may be useful in colon cancer prevention when used alone or in combination with SS or other chemopreventive agents.
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