Antitumor activity of histone deacetylase inhibitor trichostatin A in osteosarcoma cells.
BACKGROUND
Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells.


METHODS
MG- 63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system.


RESULTS
MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner.


CONCLUSIONS
Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.
Department of Orthopeadics, Sixth People's Hospital, Shanghai JiaoTong University, Shanghai, China.
Dong-Dong
DD
Cheng
Qing-Cheng
QC
Yang
Zhi-Chang
ZC
Zhang
Cui-Xia
CX
Yang
Yi-Wen
YW
Liu
D017304:Annexin A5 / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D017304:Annexin A5; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A