2. Academic Validation
  3. Epigenetic modulation with HDAC inhibitor CG200745 induces anti-proliferation in non-small cell lung cancer cells

Epigenetic modulation with HDAC inhibitor CG200745 induces anti-proliferation in non-small cell lung cancer cells

  • PLoS One. 2015 Mar 17;10(3):e0119379. doi: 10.1371/journal.pone.0119379.
Sung-Min Chun 1,  Ji-Young Lee 2,  Jene Choi 1,  Je-Hwan Lee 3,  Jung Jin Hwang 2,  Chung-Soo Kim 4,  Young-Ah Suh 2,  Se Jin Jang 5
Affiliations

Affiliations

  • 1 Department of Pathology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 2 Asan Institute for Life Science, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 3 Department of Oncology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 4 Department of Urology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 5 Department of Pathology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea; Asan Institute for Life Science, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.
PMID: 25781604 DOI: 10.1371/journal.pone.0119379
Abstract

Histone modification plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes. Hence, chemical approaches targeting histone-modifying Enzymes have emerged onto the main stage of Anticancer drug discovery. Here, we investigated the therapeutic potentials and mechanistic roles of the recently developed histone deacetylase inhibitor, CG200745, in non-small cell lung Cancer cells. Treatment with CG200745 increased the global level of histone acetylation, resulting in the inhibition of cell proliferation. ChIP-on-chip analysis with an H4K16ac antibody showed altered H4K16 acetylation on genes critical for cell growth inhibition, although decreased at the transcription start site of a subset of genes. Altered H4K16ac was associated with changes in mRNA expression of the corresponding genes, which were further validated in quantitative RT-PCR and western blotting assays. Our results demonstrated that CG200745 causes NSCLC cell growth inhibition through epigenetic modification of critical genes in Cancer cell survival, providing pivotal clues as a promising chemotherapeutics against lung Cancer.

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