OBJECTIVE In prostate cancer(PCa),signal transducer and activator of transcription factor3(STAT3)has been strongly associated with tumor progression,through numerous means.Hence this allows STAT3 to be an important target for therapeutic action.Artesunate(ART),a well know antimalarial agentis making its way as an anticancer drug.In the present study,we investigated whether ART can control aberrant STAT3 signaling,and thereby take a toll on PCa development.METHODS Various PCa cell lines(DU145,PC3,LNCaP)and in vivo xenograft mouse model are used.Cytotoxic effects of ART against various PCa cell lines were evaluated by MTT assay.Flow cytometry cell cycle analysis and DNA fragmentation assay was done to detect the apoptotic effect of ART.Expression of STAT3 and its regulated gene in the presence and absence of ART were measured by WB,IHC and RT PCR.STAT3 DNA binding activities was analyzed by ELISA.RESULTS ART was found to dephosphorylate STAT3 at Tyr 405,thereby reducing its nuclear translocation and DNA binding efficiency in DU145 PCa cells.We 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 lines.Furthermore,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 ART.We observed reversal in ART mediated inhibition of STAT3 in the presence of pervanadate,tyrosine phosphates inhibitor and during SHP-1 knock down.ART was able to inactivate STAT3 in DU145 cells exposed to conditioned media(CM)rich in cytokines.In the presence of ART we observed the down regulation of various STAT3 regulated gene products which are involved in proliferation,survival,and angiogenesis.ART even blocked the motility and invasion of PCa cells.ART substantially decreased the tumor volume in xenograft mouse which is implanted with DU145 cells.Also ability of ART to control aberrant STAT3 signaling was in accordance with its invitrostudies.CONCLUSION Over all through our findings,we have disclosed for the first time that ART could possibly exerts it antitumor effect by interrupting deregulated expression of STAT3 in PCa,both in vitro and in vivo. OBJECTIVE In prostate cancer (PCa), signal transducer and activator of transcription factor 3 (STAT3) has been strongly associated with tumor progression, through numerous means .ence this this STAT 3 to be important target for therapeutic action. Artesunate (ART), a well know antimalarial agentis making its way as an anticancer drug. in the present study, we investigating whether ART can control aberrant STAT3 signaling, and thus take toll on PCa development. METHODS Various PCa cell lines (DU 145, PC3, LNCaP) and in vivo xenograft mouse models are used. Cytotoxic effects of ART against various PCa cell lines were evaluated as by MTT assay. Flow cytometry cell cycle analysis and DNA fragmentation assay was done to detect the apoptotic effect of ART. Expression of STAT3 and its regulated gene in the presence and absence of ART were measured by WB, IHC and RT PCR. STAT3 DNA binding activities were analyzed by ELISA .RESULTS ART was found to dephosphorylate STAT3 at Tyr 405, thereby reducing its nuclear trans location and DNA binding efficiency in DU145 PCa cells. We proclaim that ART could prevent the PCa development, as it can inhibit proliferation, bring about cell cycle arrest at G0 / G1 phase, Annexin Ⅴ positive staining, DNA fragmentation, caspase 3 activation and PARP cleavage in Inhibition of constitutive STAT3 expression was associated with the ability of ART to suppress its upstream kinases such as Janus kinase 1 and 2 (JAK1 and 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 ART. We observed reversal in ART mediated inhibition of STAT3 in the presence of pervanadate, tyrosine phosphates inhibitor and during SHP-1 knock down. FET was able to inactivate STAT3 in DU 145 cells exposed to conditioned media (CM) rich in cytokines. in the presence of ART we observed the down regulation of various STAT3 regulated gene products which are involved in proliferation, survival, an dATPase. even even the tumor volume in xenograft mouse which is implanted with DU145 cells. Ability to ART to control aberrant STAT3 signaling was in accordance with its invitrostudies. CONCLUSION Over all through our findings, we have disclosed for the first time that ART could exert it it antitumor effect by interrupting deregulated expression of STAT3 in PCa, both in vitro and in vivo.