Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Trichostatin A induces apoptosis in lung cancer cells viasimultaneous activation of the death receptor-mediated andmitochondrial pathway

Kim, Hak-Ryeol;Kim, Eun-Jeong;Yang, Se-Hun;Jeong, Eun-Taek;Park, Chae-Ni;Lee, Jae-Hyeong;Yun, Myeong-Ja;So, Hong-Seop;Park, Rae-Gil
김학렬;김은정;양세훈;정은택;박채니;이재형;윤명자;소홍섭;박래길

  • Published : 20060000
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Abstract

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.

Keywords

References

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