Resveratrol analog, N-(4-methoxyphenyl)-3,5-dimethoxybenzamide induces G2/M phase cell cycle arrest and apoptosis in HeLa human cervical cancer cells

Abstract

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.

Keywords: Antiproliferation; Apoptosis; G2/M arrest; N-(4-Methoxyphenyl)-3,5-dimethoxybenamide; Resveratrol.