HIF-1 alpha induced by beta-elemene protects human osteosarcoma cells from undergoing apoptosis

作者：Liang Dan; Yang Maowei^*; Guo Baolei; Yang Lei; Cao Junjun; Zhang Xiuli

来源：Journal of Cancer Research and Clinical Oncology, 2012, 138(11): 1865-1877.

DOI：10.1007/s00432-012-1256-5

• HIF-1 alpha
• beta-Elemene
• PI3K/Akt/mTor
• ROS
• Apoptosis
• Osteosarcoma

beta-Elemene, isolated from more than 50 Chinese herbs and plants, has shown promising anticancer effects against a broad spectrum of tumors, such as lung, breast, prostate, cervical, colon and ovarian carcinomas (Wang et al. in Cell Mol Life Sci 62:881-893, 2005; Li et al. in Cell Mol Life Sci 62:894-904, 2005; J Pharm Pharmacol 62(8):1018-1027, 2010). But it has not reported in osteosarcoma cells. The aim of the present study is to investigate the antitumor effect of beta-elemene on human osteosarcoma cancer cells and the molecular mechanism involved.
beta-Elemene inhibited the viability of human osteosarcoma cells in a dose-time-dependent manner. The suppression of cell viability was due to the induction of apoptosis. Our study also found that beta-elemene treatment upregulated HIF-1 alpha protein, which partially inhibits apoptosis. Knockdown of HIF-1 alpha with small interfering RNA or co-treatment with the HIF-1 alpha inhibitor YC-1 significantly enhanced the antitumor effects of beta-elemene.
Our study first found that beta-elemene could increase the expression of HIF-1 alpha through ROS and PI3K/Akt/mTor signaling pathway. And HIF-1 alpha partially prevents human osteosarcoma cells from undergoing apoptosis. The anticancer effects of beta-elemene was weakened by HIF-1 alpha. So, we recognize that a combination of beta-elemene with HIF-1 alpha inhibitor might be a useful therapeutic option for osteosarcoma.

• 出版日期2012-11
• 单位中国医科大学