Department of Pharmacology, Qiqihar Medical University, Qiqihar 161006, PR China.
Oncol Rep. 2012 Jun;27(6):1976-80. doi: 10.3892/or.2012.1717. Epub 2012 Mar 12.
The phosphoinositol-3-kinase (PI3K)/Akt signal transduction pathway is critically important for tumor cell growth, proliferation and apoptosis. Apoptosis activation has been reported to be a good target in cancer therapies. In this study, we have found that jolkinolide B (JB), a diterpenoid from the traditional Chinese medicinal herb Euphorbia fischeriana Steud, strongly inhibited the expression of the PI3K p85 subunit and the phosphorylation of Akt. Furthermore, we evaluated the effects of 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 incubated with JB. This effect was enhanced by combination with LY294002. In addition, treatment with JB could induce downregulation of the Bcl-2/Bax ratio, and subsequent promotion of 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 apoptosis in JB-treated cells. These observations suggest that JB may have therapeutic applications in the treatment of cancer.
磷酸肌醇-3-激酶（PI3K）/ Akt 信号转导通路对肿瘤细胞的生长、增殖和凋亡至关重要。凋亡激活已被报道为癌症治疗的一个良好靶点。在这项研究中，我们发现从传统中药大戟属植物 Euphorbia fischeriana Steud 中提取的二萜 Jolkinolide B（JB）强烈抑制 PI3K p85 亚基的表达和 Akt 的磷酸化。此外，我们评估了 JB 对 MDA-MB-231 人乳腺癌细胞增殖和凋亡的影响。我们的结果表明，JB 孵育可显著诱导 MDA-MB-231 细胞凋亡。这种作用通过与 LY294002 联合增强。此外，JB 处理可诱导 Bcl-2/Bax 比值下调，随后促进线粒体细胞色素 c 释放和 caspase-3 激活。总之，JB 诱导 MDA-MB-231 细胞凋亡是通过线粒体途径发生的。此外，PI3K/Akt 信号级联在 JB 处理细胞中的凋亡诱导中起作用。这些观察结果表明，JB 可能在癌症治疗中有治疗应用。
