A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway.
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.
Department of Clinical Laboratory and Medical Research Center, Zhuhai Hopital of Jinan University, Zhuhai People's Hospital, Zhuhai, 519000, China.|Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China.
Pinghong
P
Ming
Shenzhen Second People's Hospital, Shenzhen, 518055, China.
Ting
T
Cai
China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
Jin
J
Li
Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China.
Yong
Y
Ning
Hubei University of Traditional Chinese Medicine, Wuhan, 430065, China.
Shengao
S
Xie
China State Institute of Pharmaceutical Industry, Shanghai, 200437, China.
Tao
T
Tao
Department of Clinical Laboratory and Medical Research Center, Zhuhai Hopital of Jinan University, Zhuhai People's Hospital, Zhuhai, 519000, China.
Faqing
F
Tang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056751:Cyclin A2 / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015394:Molecular Structure; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C000625921:7-hydroxy-5,4'-dimethoxy-2-phenylbenzofuran; D001572:Benzofurans; D056751:Cyclin A2; D010936:Plant Extracts; D011494:Protein Kinases; D051357:Cyclin-Dependent Kinase 2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C105430:benzofuran
apoptosis; arylbenzofuran; cell cycle; cervical cancer; mitochondria