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

被引:31
作者
Wang, Xiao-fang [1 ]
Wang, Jun [2 ]
机构
[1] Beijing Army Gen Hosp, Dept Pharm, Beijing 100700, Peoples R China
[2] Tsinghua Univ, Med Ctr, Dept Traumatol, Beijing 100035, Peoples R China
关键词
osteosarcoma; icaritin; apoptosis; MMP-2; MMP-9; caspase-3; zVAD-fmk; EMBRYONIC STEM-CELLS; TUMOR MICROENVIRONMENT; SIGNALING PATHWAYS; ESTROGEN-RECEPTOR; INHIBITION; DIFFERENTIATION; INVASIVENESS; CARCINOMA; KNOCKDOWN; S100A4;
D O I
10.1038/aps.2013.178
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 SaOS(2) 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 mu mol/L) suppressed the proliferation of SaOS(2) cells in vitro in a dose-dependent manner. Furthermore, the cell motility was significantly decreased after exposure to icaritin. Moreover, icaritin (5 mu mol/L) time-dependently induced the apoptosis of SaOS(2) 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 mu mol/L) compromised the icaritininduced caspase-3 expression and apoptosis in SaOS(2) cells. Conclusion: Icaritin suppresses the proliferation of SaOS(2) human osteosarcoma cells by increasing apoptosis and downregulating MMP expression.
引用
收藏
页码:531 / 539
页数:9
相关论文
共 41 条
[1]   Hypoxia-Induced Cytotoxic Drug Resistance in Osteosarcoma Is Independent of HIF-1Alpha [J].
Adamski, Jennifer ;
Price, Andrew ;
Dive, Caroline ;
Makin, Guy .
PLOS ONE, 2013, 8 (06)
[2]   Radiosensitization by histone deacetylase inhibition in an osteosarcoma mouse model [J].
Blattmann, C. ;
Thiemann, M. ;
Stenzinger, A. ;
Christmann, A. ;
Roth, E. ;
Ehemann, V. ;
Debus, J. ;
Kulozik, A. E. ;
Weichert, W. ;
Huber, P. E. ;
Oertel, S. ;
Abdollahi, A. .
STRAHLENTHERAPIE UND ONKOLOGIE, 2013, 189 (11) :957-+
[3]   Runx2 in normal tissues and cancer cells: A developing story [J].
Blyth, Karen ;
Vaillant, Francois ;
Jenkins, Alma ;
McDonald, Laura ;
Pringle, Marie Anne ;
Huser, Camille ;
Stein, Torsten ;
Neil, James ;
Cameron, Ewan R. .
BLOOD CELLS MOLECULES AND DISEASES, 2010, 45 (02) :117-123
[4]   Icaritin induces growth inhibition and apoptosis of human prostatic smooth muscle cells in an estrogen receptor-independent manner [J].
Chen, Min-Feng ;
Qi, Lin ;
Li, Yuan ;
Zu, Xiong-Bing ;
Dai, Yuan-Qin ;
Zhang, Peng .
AMINO ACIDS, 2010, 38 (05) :1505-1513
[5]   Inhibition of the STAT3 signaling pathway is involved in the antitumor activity of cepharanthine in SaOS2 cells [J].
Chen, Zan ;
Huang, Chen ;
Yang, Yan-ling ;
Ding, Yi ;
Ou-Yang, Han-qiang ;
Zhang, You-yi ;
Xu, Ming .
ACTA PHARMACOLOGICA SINICA, 2012, 33 (01) :101-108
[6]   An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells [J].
Guo, YuMing ;
Zhang, XinTian ;
Meng, Jun ;
Wang, Zhao-Yi .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2011, 658 (2-3) :114-122
[7]   Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma. patients [J].
Han, Ju ;
Tian, Rui ;
Yong, Bicheng ;
Luo, Canqiao ;
Tan, Pingxian ;
Shen, Jingnan ;
Peng, Tingsheng .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 435 (03) :493-500
[8]   Caspase-independent apoptosis induction of quorum-sensing autoinducer analogs against chronic myeloid leukemia K562 [J].
Hazawa, Masaharu ;
Kudo, Michiko ;
Iwata, Toshihiro ;
Saito, Kazuki ;
Takahashi, Kenji ;
Igarashi, Jun ;
Suga, Hiroaki ;
Kashiwakura, Ikuo .
INVESTIGATIONAL NEW DRUGS, 2012, 30 (03) :862-869
[9]   Icaritin Induces Apoptosis of HepG2 Cells via the JNK1 Signaling Pathway Independent of the Estrogen Receptor [J].
He, Jun ;
Wang, Yan ;
Duan, Fei ;
Jiang, Hao ;
Chen, Min-Feng ;
Tang, Si-Yuan .
PLANTA MEDICA, 2010, 76 (16) :1834-1839
[10]   Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro [J].
Huang, Jian ;
Yuan, Lan ;
Wang, Xi ;
Zhang, Tian-Lan ;
Wang, Kui .
LIFE SCIENCES, 2007, 81 (10) :832-840