In vitro and in vivo effect of artesunate against prostate cancer:Targetting STAT3 pathway to combat disease progression

作     者：NachiyappanALAMELU KwangSeokAHN KodappullySivaramanSIVEEN AlanPremKUMAR GautamSETHI 

作者机构：Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 College of Oriental Medicine Kyung Hee University Seoul 130-701 Republic of Korea Cancer Science Institute of Singapore Centre for Translational Medicine Singapore 117599 School of Biomedical Sciences Faculty of Health Sciences Curtin University Western Australia 6009 Australia Department of Biological Sciences University of North Texas Denton TX 76203 USA 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2015年第29卷第S1期

页      面：81-82页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

主　　题：antitumor DU145 JAK SHP-1 

摘      要：OBJECTIVE In prostate cancer(PCa),signal transducer and activator of transcription factor3(STAT3)has been strongly associated with tumor progression,through numerous *** this allows STAT3 to be an important target for therapeutic ***(ART),a well know antimalarial agentis making its way as an anticancer *** the present study,we investigated whether ART can control aberrant STAT3 signaling,and thereby take a toll on PCa *** Various PCa cell lines(DU145,PC3,LNCaP)and in vivo xenograft mouse model are *** effects of ART against various PCa cell lines were evaluated by MTT *** cytometry cell cycle analysis and DNA fragmentation assay was done to detect the apoptotic effect of *** of STAT3 and its regulated gene in the presence and absence of ART were measured by WB,IHC and RT ***3 DNA binding activities was analyzed by *** ART was found to dephosphorylate STAT3 at Tyr 405,thereby reducing its nuclear translocation and DNA binding efficiency in DU145 PCa *** proclaim that ART can prevent the PCa development,as it can inhibit proliferation,bring about cell cycle arrest at G0/G1 phase,AnnexinⅤ positive staining,DNA fragmentation,caspase 3activation and PARP cleavage in PCa cell ***,inhibition of constitutive STAT3 expression was associated with the ability of ART to suppress its upstream kinases such as Janus kinase 1and 2(JAK1and JAK2).SHP-1,protein tyrosine phosphatases which are considered to be one of the major regulators of STAT3 phosphorylation was upregulated in the presence of *** observed reversal in ART mediated inhibition of STAT3 in the presence of pervanadate,tyrosine phosphates inhibitor and during SHP-1 knock *** was able to inactivate STAT3 in DU145 cells exposed to conditioned media(CM)rich in *** the presence of ART we observed the down regulation of various STAT3 regulated gene products which are involved in proliferation,survival,and