Apoptosis-Inducing Effect of Garcinol Is Mediated by NF-κB Signaling in Breast Cancer Cells

Garcinol, obtained from Garcinia indica in tropical regions, is used for its numerous biological effects. Its anti-cancer activity has been suggested but the mechanism of action has not been studied in-detail, especially there is no report on its action against breast cancer cells. Here we tested our hypothesis that garcinol may act as an anti-proliferative and apoptosis-inducing agent against breast cancer cell lines. Using multiple techniques such as mTT, Histone-DNA ELISA, Annexin V-PI staining, Western blot for activated caspases and cleaved PARP, homogenous caspase-3/7 fluorornetric assay and EMSA, we investigated the mechanism of apoptosis-inducing effect of garcinol in ER-positive MCF-7 and ER-negative MDA-MB-231 cells. We found that garcinol exhibits dose-dependent cancer cell-specific growth inhibition in both the cell lines with a concomitant induction of apoptosis, and has no effect on non-tumorigenic MCF-10A cells. Our results suggested induction of caspase-mediated apoptosis in highly metastatic MDA-MB-231 cells by garcinol. Down-regulation of NF-kappa B signaling pathway was observed to be the mechanism of apoptosis-induction. Garcinol inhibited constitutive NF-kappa B activity, which was consistent with down-regulation of NE-kappa B-regulated genes. This is the first report on anti-proliferative and apoptosis-inducing action of garcinol against human breast cancer cells and the results suggest that this natural compound merits investigation as a potential chemo-preventive/-therapeutic agent, especially against breast cancer. J. Cell. Biochem. 109: 1134-1141, 2010. (C) 2010 Wiley-Liss, Inc.