Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways

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.