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  • Title: Apoptosis-inducing effect of garcinol is mediated by NF-kappaB signaling in breast cancer cells.
    Author: Ahmad A, Wang Z, Ali R, Maitah MY, Kong D, Banerjee S, Padhye S, Sarkar FH.
    Journal: J Cell Biochem; 2010 Apr 15; 109(6):1134-41. PubMed ID: 20108249.
    Abstract:
    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 fluorometric 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-kappaB signaling pathway was observed to be the mechanism of apoptosis-induction. Garcinol inhibited constitutive NF-kappaB activity, which was consistent with down-regulation of NF-kappaB-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.
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