OBJECTIVE The present study was designed to investigate anticancer effect of zeylenone(Zey)on K562 cells derived from chronic myelogenous leukemia(CML)both in vitro and in vivo,followed by exploring the underlying mechanisms.METHODS Initially,the effects of Zey on cel viability,proliferation,and apoptosis were measured in K562 cells by MTT,soft agar assay,AO/EB staining,hoechst 33258 staining and flow cytometric analysis after they were treated with Zey for indicated time,the involving signaling pathways were then investigated by JC-1,real-time quantitative polymerase chain reaction(RT-q PCR),Western blotting and immunofluorescence analysis.Furthermore,the in vivo anti-tumoractivity of Zey was assessed with nude xenografts and the involving mechanism was confirmed by immunohistochemical(IHC)and histopathological analysis.RESULTS We identified that Zey dose-dependently decreased cell viability,colony formation and expression of Proliferating Cell Nuclear Antigen(PCNA),and significantly induced K562 cell apoptosis via regulating Bcl-2 family members,decreasing mitochondrial transmembrane potential,and activating caspase-3,caspase-9,and caspase-8(P<0.05 or P<0.01).Further study revealed that Zey significantly inhibited phosphorylation of Jak2 and Src and downregulated their downstream proteins,including stat3,PI3K/AKT/m TOR,and ERK1/2 signaling pathways(P<0.05 or P<0.01).Zey also suppressed tumor growth with low toxicity in mouse xenograft model of K562cells through decreasing expression of Jak2 and Src.CONCLUSION Our data demonstrated that Zey substantially suppressed K562 cells both in vitro and in vivo through Jak2 and Src pathways.These findings suggest the potential of Zey as an effective anticancer agent in CML treatment. OBJECTIVE The present study was designed to investigate anticancer effect of zeylenone (Zey) on K562 cells derived from chronic myelogenous leukemia (CML) both in vitro and in vivo, followed by exploring the underlying mechanisms. METHODS Initially, the effects of Zey on cel viability , proliferation, and apoptosis were measured in K562 cells by MTT, soft agar assay, AO / EB staining, hoechst 33258 staining and flow cytometric analysis after they were treated with Zey for indicated time, the involving signaling pathways were then investigated by JC-1 , the real-time quantitative polymerase chain reaction (RT-q PCR), Western blotting and immunofluorescence analysis. Future in vivo anti-tumoractivity of Zey was assessed with nude xenografts and the involvement mechanism was confirmed by immunohistochemical (IHC) and histopathological analysis .RESULTS We identified that Zey dose-dependently decreased cell viability, colony formation and expression of Proliferating Cell Nuclear Antigen (PCNA), and significantly induced K562 cell apoptosis via regulating Bcl-2 family members, decreasing mitochondrial transmembrane potential, and activating caspase-3, caspase-9, and caspase-8 (P <0.05 or P <0.01). Further research revealed that Zey significantly inhibited phosphorylation of Jak2 and Src and downregulated their downstream proteins including stat3, PI3K / AKT / m TOR, and ERK1 / 2 signaling pathways (P <0.05 or P <0.01) .Zey also suppressed tumor growth with low toxicity in mouse xenograft model of K562 cells through decreasing expression of Jak2 and Src.CONCLUSION Our dataiform that Zey substantially suppressed K562 cells both in vitro and in vivo through Jak2 and Src pathways. These findings suggest the potential of Zey as an effective anticancer agent in CML treatment.