A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway
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Pinghong Ming1,2,*, Ting Cai3,*, Jin Li4,*, Yong Ning2, Shengao Xie2, Tao Tao4, Faqing Tang1
1Department of Clinical Laboratory and Medical Research Center, Zhuhai Hopital of Jinan University, Zhuhai People’s Hospital, Zhuhai, 519000, China
2Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China
3Shenzhen Second People's Hospital, Shenzhen, 518055, China
4China State Institute of Pharmaceutical Industry, Shanghai, 200437, China
*These authors contributed equally to this work
Faqing Tang, email: firstname.lastname@example.org
Keywords: cervical cancer, arylbenzofuran, apoptosis, mitochondria, cell cycle
Received: January 20, 2016 Accepted: May 12, 2016 Published: May 31, 2016
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.
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