Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garciniahanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including anA549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mousemodels to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-relatedproteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins inMDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressedbreast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax,as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and inducedcell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenicacid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor andmitochondrial pathways in vivo and in vitro.
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