1. Antiproliferative effects of S-allylmercaptocysteine on colon cancer cells when tested alone or in combination with sulindac sulfide.
- Author
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Shirin H, Pinto JT, Kawabata Y, Soh JW, Delohery T, Moss SF, Murty V, Rivlin RS, Holt PR, and Weinstein IB
- Subjects
- Apoptosis drug effects, Blotting, Western, Caspase 3, Caspases drug effects, Caspases metabolism, Cell Cycle drug effects, Cysteine chemistry, Dose-Response Relationship, Drug, Enzyme Activation drug effects, G2 Phase drug effects, Garlic chemistry, Glutathione drug effects, Glutathione metabolism, HT29 Cells, Humans, In Situ Hybridization, Fluorescence, Isoenzymes metabolism, JNK Mitogen-Activated Protein Kinases, Kinetics, Mitogen-Activated Protein Kinases metabolism, Mitosis drug effects, Plants, Medicinal, Proto-Oncogene Proteins c-bcl-2 drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Sulindac analogs & derivatives, Tumor Cells, Cultured cytology, Tumor Cells, Cultured drug effects, Tumor Cells, Cultured metabolism, Antineoplastic Agents pharmacology, Cell Division drug effects, Cysteine analogs & derivatives, Cysteine pharmacology, Sulindac pharmacology
- Abstract
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.
- Published
- 2001