A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway

// Pinghong Ming 1, 2, * , Ting Cai 3, * , Jin Li 4, * , Yong Ning 2 , Shengao Xie 2 , Tao Tao 4 , Faqing Tang 1 1 Department of Clinical Laboratory and Medical Research Center, Zhuhai Hopital of Jinan University, Zhuhai People’s Hospital, Zhuhai, 519000, China 2 Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China 3 Shenzhen Second People's Hospital, Shenzhen, 518055, China 4 China State Institute of Pharmaceutical Industry, Shanghai, 200437, China * These authors contributed equally to this work Correspondence to: Faqing Tang, email: tangfaqing33@hotmail.com Keywords: cervical cancer, arylbenzofuran, apoptosis, mitochondria, cell cycle Received: January 20, 2016      Accepted: May 12, 2016      Published: May 31, 2016 ABSTRACT 7-hydroxy-5,4′-dimethoxy-2-arylbenzofuran (Ary) is purified from Livistona. It has been demonstrated to have anticancer activity to various tumors in including cervical cancer, but its mechanism is still unclear. In the present, we show that Ary induces cervical cancer cells apoptosis through mitochondria degradation and mediates cervical cancer cell arrest. Further, Ary-inducing cell cycle G1/S-phase arrest is associated with increased cyclin A2 and cyclin dependent kinase 2 (Cdk2) proteins. Knockdown of cyclin A2 using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced G1/S-phase arrest. Moreover, Ary sustainedly induced phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2). And ERK1/2 phosphorylation inhibition using specific inhibitor U0126 effectively suppressed cyclin A2 expression, and reduced G1/S-phase arrest induced by Ary. All the experiments in vitro and in vivo verified that Ary has an anticancer effect on cervical cancer. These data provide novel evidences that Ary induces cervical cancer cells apoptosis through mitochondria degradation and cell G1/S-phase arrest. These findings also suggest that ERK-mediated Cdk2/cyclin A signaling pathway is involved in Ary-induced G1/S-phase arrest.