HIF-1α induced by β-elemene protects human osteosarcoma cells from undergoing apoptosis.
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.
Department of Orthopedics, The First Affiliated Hospital, China Medical University, No 155 Nanjing North Street, Shenyang, Liaoning, People's Republic of China.
Dan
D
Liang
Maowei
M
Yang
Baolei
B
Guo
Lei
L
Yang
Junjun
J
Cao
Xiuli
X
Zhang
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
D002867:Chromones; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D058570:TOR Serine-Threonine Kinases; C445979:beta-elemene; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human