Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2.

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. However, its mechanism of action still remains unclear. In this study, we have focused primarily on the cytotoxic effects of curcumin on three human tumor cell lines and rat primary hepatocytes. Curcumin induced apoptosis in MCF-7, MDAMB, and HepG2 cells in a dose-dependent and time-dependent manner. Apoptosis was mediated through the generation of reactive oxygen species. Attempts were made to establish the role played by endogenous glutathione on the apoptotic activity of curcumin. Depletion of glutathione by buthionine sulfoximine resulted in the increased generation of reactive oxygen species, thereby further sensitizing the cells to curcumin. Interestingly, curcumin had no effect on normal rat hepatocytes, which showed no superoxide generation and therefore no cell death. These observations suggest that curcumin, a molecule with varied actions, could be developed into an effective chemopreventive and chemotherapeutic agent.