title: Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling.
abstract: Oxymatrine (OMT), a natural quinolizidine alkaloid, has been known to have anti-inflammation, anti-anaphylaxis, and chemopreventive effects on various cancer cells. To clarify the underlying role and molecular mechanisms of OMT in human hemangioma (HA), in the present study, we examined the expression of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) in different phases of human HA. After HA derived endothelial cells (HDEC) were pretreated with different concentrations of OMT, cell proliferation, apoptosis, and cycle distribution were evaluated by MTT assay and flow cytometry analysis, respectively. The effects of OMT on expression of HIF-1a signaling were determined by real-time PCR and western blot assays. Our results showed that, the expression of HIF-1a and VEGF was significantly increased in proliferating phase HA, but decreased in involuting phase HA. Moreover, OMT in vitro inhibited proliferative activities and induced cell apoptosis and cycle arrest in G0/G1 phase in HA cells with decreased expression of HIF-1a, VEGF, Bcl-2, and CyclinD1, and increased expression of p53. Taken together, our findings suggest that, the expression of HIF-1a and VEGF is increased in proliferating phase HA, and OMT suppresses cell proliferation and induces cell apoptosis and cycle arrest in proliferative phase HA through inhibition of the HIF-1a signaling pathway, suggesting OMT may provide a novel therapeutic strategy for the treatment of HA.
authors: Department of General Surgery, Xinhua Hospital (Chong Ming) affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: Z-W
authors: ZW
authors: Fei
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: M-K
authors: MK
authors: Qiu
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: X-Q
authors: XQ
authors: Qi
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: Y-X
authors: YX
authors: Dai
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: S-Q
authors: SQ
authors: Wang
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: Z-W
authors: ZW
authors: Quan
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors: Y-B
authors: YB
authors: Liu
authors: Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, PR China oujingmin1501@163.com.
authors: J-M
authors: JM
authors: Ou
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006391:Hemangioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011807:Quinolizines; D042461:Vascular Endothelial Growth Factor A; C497442:HIF1A protein, human; C037573:oxymatrine; D000093842:Matrines
keywords: HIF-1a; apoptosis; hemangioma; oxymatrine; proliferation