| Summary: | 碩士 === 高雄醫學大學 === 天然藥物研究所碩士班 === 94 === This study first investigates the anticancer effect of plumbagin in human non-small cell lung cancer cells, A549. Plumbagin has exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21 in a p53-dependent manner, and reduced amounts of cyclin B1, cdc2 and cdc25C. Plumbagin treatment also enhanced the levels of inactivated phosphorylated cdc2 and cdc25C. Blockade of p53 activity by dominant negative p53 transfection partially decreased plumbagin-induced apoptosis and G2/M arrest, suggesting it might be operated by p53-dependent and independent pathway. Plumbagin treatment triggered the mitochondrial apoptotic pathway indicated by changing Bax/Bcl-2 ratios, resulting in MMP loss, cytochrome c release and caspase-9 activation. Activation of JNK by plumbagin phosphorylated p53 at Ser15 results in increasing the stabilization of p53 by decreasing p53 and MDM2 interaction. SP600125, a specific inhibitor of JNK, significantly decreased apoptosis by inhibition on the phosphorylation of p53 (Ser15), and subsequent increasing the interaction of p53 and MDM2. SP6000125 also inhibited the phosphorylation of Bcl-2 induced by plumbagin. Furthermore, plumbagin’s inhibition of cell growth effect was also evident in a nude mice model. Taken together, these results suggest a critical role for JNK1/2 and p53 in plumbagin-induced G2/M arrest and apoptosis of A549 cells.
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