KMID : 1140120060110030205
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Cancer Prevention Research 2006 Volume.11 No. 3 p.205 ~ p.210
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Combined Treatment of Trichostatin A and Heat Shock Increases Apoptosis in STAT3 dependent Astrocytoma Cells
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Baek Sun-Yong
Kim Su-Ryun Hwang Jee-Won Bae Moon-Kyoung Wee Hee-Jun Choi Yung-Hyun Oh Sae-Ock Kim Bong-Seon Yoon Sik Bae Soo-Kyung Kim Jae-Bong
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Abstract
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Trichostatin A (TSA) shows a promising therapeutic effect on cancer cells when combined with radiotherapy or chemotherapy. However, so far, little has been reported on the combined treatment with TSA and hyperthermia (heat shock: HS). Here, we examined the effect of TSA/HS on human astrocytoma A172 cells and found that TSA/HS cotreatment effectively induced apoptotic cell death. The molecular mechanism of this effect consists of reduction in the levels of antiapoptotic factors (Bcl-2 and XIAP), Hsp27, and phosphorylated STAT3 (Tyr705), a transcription factor required for survival of A172 cells. Reduction of STAT3 activity resulted in the down-regulation of its taget genes, Bcl-xL and VEGF. In contrast, the level of p53 tumor suppressor was increased by TSA/HS. Therefore, our results show that co-treatment of TSA and HS play a role as an effective inducer of apoptosis in STAT3- dependent tumor cells such as A172 cells.
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KEYWORD
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Trichostatin A, Hyperthermia, Apoptosis, STAT3, VEGF
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