Add time:08/04/2019         Source:sciencedirect.com

In this study, several resveratrol analogs were synthesized and evaluated in search of a more effective anti-proliferative resveratrol analog. Among the evaluated resveratrol analogs, we have identified N-(4-methoxyphenyl)-3,5-dimethoxybenamide (MPDB) as a potent anti-proliferative compound. Treatment with MPDB resulted in G2/M phase cell cycle arrest, which was accompanied by alteration of G2/M-related protein expression and phosphorylation. MPDB-induced G2/M arrest was blocked by transfection of ATM/ATR siRNAs, indicating the critical role of ATM/ATR in G2/M phase arrest. In addition, treatment with MPDB displayed the activation of caspase and decreased Bcl-xl protein expression after 20 h in HeLa cells. Moreover, MPDB increased cytosolic cytochrome c release and Fas and Fas-L protein expression, indicating intrinsic and extrinsic apoptosis pathway, respectively. These results suggest that MPDB is a new and potent compound that induces ATM/ATR-dependent G2/M phase cell cycle arrest and apoptosis, implicating it as a putative candidate in the investment of cervical cancer therapy.

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