title: Jolkinolide B from Euphorbia fischeriana Steud induces in human leukemic cells apoptosis via JAK2/STAT3 pathways.
abstract: Jolkinolide B from the roots of Euphorbia fischeriana Steud exhibits significant antitumor activities against several tumor lines. Previous study has shown that Jolkinolide B could induce apoptosis in human leukemia cells. However, the exact mechanism and signaling pathway involved in Jolkinolide B-induced apoptosis have not been fully elucidated. In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in dose- and time-dependent manner in human leukemic HL-60 and THP-1 cells. The induction of apoptosis was accompanied by the downregulation of JAK2/STAT3. Our results also suggest that expression of Bcl-2 and mitochondrial cytochrome c was dosedependently reduced following Jolkinolide B-treated THP-1 and HL-60 cells, whereas Jolkinolide B up-regulated the expression of Bax and cytosolic cytochrome c. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3, -8, and -9. JSI-124, a STAT-3 inhibitor, was able to block the negative effect of Jolkinolide B on cell apoptosis. Taken together, our study for the first time suggests that Jolkinolide B is able to enhance apoptosis of human leukemic HL-60 and THP-1 cells, at least in part, through downregulation of JAK2/STAT3 and bcl-2, and upregulation of Bax and cytosolic cytochrome c. Moreover, the triggering of caspase-3, -8, and -9 activation mediated apoptotic induction.
authors.affiliation: Department of Geriatrics, China Medical University, Shenyang, China. wangjh1@sj-hospital.org
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Niu
authors.forename: Lin-Hua
authors.initials: LH
authors.lastname: Shu
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Yue
authors.forename: Dong- Yang
authors.initials: D
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004224:Diterpenes; D050796:STAT3 Transcription Factor; C057914:jolkinolide B; D053614:Janus Kinase 2; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9