HIF-1α induced by β-elemene protects human osteosarcoma cells from undergoing apoptosis.

Abstract

BACKGROUND:

β-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 β-elemene on human osteosarcoma cancer cells and the molecular mechanism involved.

RESULTS:

β-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 β-elemene treatment upregulated HIF-1α protein, which partially inhibits apoptosis. Knockdown of HIF-1α with small interfering RNA or co-treatment with the HIF-1α inhibitor YC-1 significantly enhanced the antitumor effects of β-elemene.

CONCLUSIONS:

Our study first found that β-elemene could increase the expression of HIF-1α through ROS and PI3K/Akt/mTor signaling pathway. And HIF-1α partially prevents human osteosarcoma cells from undergoing apoptosis. The anticancer effects of β-elemene was weakened by HIF-1α. So, we recognize that a combination of β-elemene with HIF-1α inhibitor might be a useful therapeutic option for osteosarcoma.

• Authors: Dan Liang, Maowei Yang, Baolei Guo, Lei Yang, Junjun Cao, Xiuli Zhang
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 11 Pg. 1865-77 (Nov 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22736026 (Publication Type: Journal Article)

Chemical References

• Chromones
• Drugs, Chinese Herbal
• Enzyme Inhibitors
• Hypoxia-Inducible Factor 1, alpha Subunit
• Indazoles
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Reactive Oxygen Species
• Sesquiterpenes
• beta-elemene
• 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• MTOR protein, human
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, genetics, metabolism)
• Indazoles (pharmacology)
• Microscopy, Fluorescence
• Morpholines (pharmacology)
• Osteosarcoma (genetics, metabolism, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• Reactive Oxygen Species (metabolism)
• Sesquiterpenes (pharmacology)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Time Factors