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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2006.1
- 수록면
- 616 - 624 (9page)
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Trichostatin A (TSA), originally developed as an antifungal agent, is one of potent histone deace-tylase (HDAC) inhibitors, which are known to cause growth arrest and apoptosis induction of trans-formed cells, including urinary bladder, breast, prostate, ovary, and colon cancers. However, the effect of HDAC inhibitors on human non-small cell lung cancer cells is not clearly known yet. Herein, we demonstrated that treatment of TSA resulted in a significant decrease of the viability of H157 cells in a dose-dependent manner, which was revealed as apoptosis accompanying with nuclear fragmen-tation and an increase in sub-G0/G1 fraction. In addition, it induced the expression of Fas/FasL, which further triggered the activation of caspase-8. Catalytic activation of caspase-9 and decreased expression of anti-aptototic Bcl-2 and Bcl-XL pro-teins were observed in TSA-treated cells. Catalytic activation of caspase-3 by TSA was further con-firmed by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxy-ribonuclease (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction, inc-luding mitochondrial membrane potential transition and release of mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells. Taken together, our data indicate that inhibition of HDAC by TSA induces the apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic and mitocondria-mediated intrinsic caspases path-way.
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참고문헌 (29)
참고문헌 신청
/ 1978 / Erythroleukemic differentiation 47 : 419 ~ 48
/ 1979 / Different accessibilities in chromatin to histone acetylase 254 : 1716 ~ 23
/ 1993 / Cell cycle-related changes in chromatin structure detected by flow cytometry using multiple DNA fluorochromes 37 : 129 ~ 38
/ 1993 / Trapoxin,an antitumor cyclic tetrapeptide,is an irreversible in-hibitor of mammalian hisone deacetylase 268 : 22429 ~ 35
/ 1994 / Trichostatin A induces morphological changes and gelsolin ex-pression by inhibiting histone deacetylase in human carcino-ma cell lines 214 : 189 ~ 97
/ 1979 / Different accessibilities in chromatin to histone acetylase 254 : 1716 ~ 23
/ 1993 / Cell cycle-related changes in chromatin structure detected by flow cytometry using multiple DNA fluorochromes 37 : 129 ~ 38
/ 1993 / Trapoxin,an antitumor cyclic tetrapeptide,is an irreversible in-hibitor of mammalian hisone deacetylase 268 : 22429 ~ 35
/ 1994 / Trichostatin A induces morphological changes and gelsolin ex-pression by inhibiting histone deacetylase in human carcino-ma cell lines 214 : 189 ~ 97
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