Matrine-induced apoptosis in Hep3B cells via the inhibition of MDM2.

Matrine, an alkaloid component derived from the Sophora root, can inhibit cancer cell proliferation and induce autophagy via p53 associated pathways. However, numerous tumor cells lack functional p53 and little is known about the effect of matrine on the p53-deficient/mutant cancer cells. The present study aimed to assess anticancer effects of matrine in p53-deficient human Hep3B hepatoma cells. The present results demonstrated that matrine caused Hep3B cell apoptosis by suppressing gene expression of minute double-mutant (MDM)2. Notably, it was revealed that matrine inhibited MDM2 at the transcriptional level in a time- and dose-dependent manner. This MDM2 inhibition resulted in induction of the p53 family member, p73; however, the functions of p73 were not induced since matrine-induced p73 failed to activate its target genes, p21 and p53 upregulated modulator of apoptosis. The matrine-induced downregulation of MDM2 led to an inhibition of inhibitor of apoptosis protein 3, which might serve a critical role in matrine-induced apoptosis in MDM2-overexpressing Hep3B cells. Finally, combination therapy of matrine with 100 µM epotoside successfully killed more Hep3B cells, suggesting that matrine can sensitize p53-deficient Hep3B cells to epotoside-induced apoptosis. [ABSTRACT FROM AUTHOR]