title: Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways.
abstract: Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud, is known to induce apoptosis in cancer cells. However, the molecular mechanism of its anti-cancer activity has not been fully elucidated. In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in a dose- and time-dependent manner in human leukemic U937. The induction of apoptosis was also accompanied by the downregulation of PI3K/Akt and the inhibitor of apoptosis protein (IAP) family proteins. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of Jolkinolide B. Taken together, our study for the first time suggest that Jolkinolide B is able to enhance apoptosis of U937 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, triggering of caspase-3 and -9 activation mediated apoptotic induction.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang 110004, PR China. wangjh1@sj-hospital.org
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Wang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhou
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020298:U937 Cells; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C057914:jolkinolide B; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D053148:Caspase 3; D053453:Caspase 9
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