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Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression

  
@article{APS8228,
	author = {Xiao-fang Wang and Jun Wang},
	title = {Icaritin suppresses the proliferation of human osteosarcoma cells  in vitro  by increasing apoptosis and decreasing MMP expression},
	journal = {Acta Pharmacologica Sinica},
	volume = {35},
	number = {4},
	year = {2016},
	keywords = {},
	abstract = {Xiao-fang WANG1, Jun WANG2, *
1Department of Pharmacy, Beijing Army General Hospital, Beijing 100700, China; 2Department of Traumatology, Medical Center Tsinghua University, Beijing Jishuitan Hospital, Beijing 100035, China
 
Aim: To explore whether icaritin, a prenylflavonoid derivative of the Chinese tonic herb Epimedium, could suppress the proliferation of human osteosarcoma cells in vitro, and to elucidate the mechanisms of the action. 
Methods: Human osteosarcoma SaOS2 cell line was used in the present study.  The proliferation of the cells was examined using MTT assay and immunofluorescence DAPI staining.  Cell motility was studied with the scratch assay.  Cell apoptosis was determined by Annexin V-FITC and PI double staining using flow cytometry.  Western blotting and RT-PCR were used to measure the expression of mRNAs and proteins in the cells. 

Results: Icaritin (5–15 μmol/L) suppressed the proliferation of SaOS2 cells in vitro in a dose-dependent manner.  Furthermore, the cell motility was significantly decreased after exposure to icaritin.  Moreover, icaritin (5 μmol/L) time-dependently induced the apoptosis of SaOS2 cells, markedly suppressed MMP-2 and MMP-9 expression, upregulated caspase-3 and caspase-9 expression, and increased the level of cleaved caspase-3 in the cells.  Co-exposure to the caspase-3 inhibitor zVAD-fmk (10 μmol/L) compromised the icaritin-induced caspase-3 expression and apoptosis in SaOS2 cells.

Conclusion: Icaritin suppresses the proliferation of SaOS2 human osteosarcoma cells by increasing apoptosis and downregulating MMP expression.

 
Keywords: osteosarcoma; icaritin; apoptosis; MMP-2; MMP-9; caspase-3; zVAD-fmk
 
This study was supported by the National Natural Science Foundation of China (No 81270968).
* To whom correspondence should be addressed. 
E-mail pkuwj2010@sina.cn
Received 2013-08-03    Accepted 2013-11-15},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/8228}
}