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The phosphoinositol-3-kinase (PI3K)/Akt signal transduction pathway is criticallyimportant for tumor cell growth, proliferation and apoptosis. Apoptosis activationhas been reported to be a good target in cancer therapies. In this study, we havefound that jolkinolide B (JB), a diterpenoid from the traditional Chinese medicinalherb Euphorbia fischeriana Steud, strongly inhibited the expression of the PI3Kp85 subunit and the phosphorylation of Akt. Furthermore, we evaluated the effectsof JB on the proliferation and apoptosis of MDA-MB-231 human breast cancer cells.Our results show significant induction of apoptosis in MDA-MB-231 cells incubatedwith JB. This effect was enhanced by combination with LY294002. In addition, treatmentwith JB could induce downregulation of the Bcl-2/Bax ratio, and subsequent promotionof mitochondrial release of cytochrome c and activation of caspase-3. Taken together,JB-induced apoptosis of MDA-MB-231 cells occurs through the mitochondrial pathway.Further, the PI3K/Akt signaling cascade plays a role in the induction of apoptosisin JB-treated cells. These observations suggest that JB may have therapeutic applicationsin the treatment of cancer.

Jolkinolide B induces apoptosis in MDA-MB-231 cells through inhibition of the PI3K/Akt signaling pathway