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

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.

• Authors: Sung-Min Chun, Ji-Young Lee, Jene Choi, Je-Hwan Lee, Jung Jin Hwang, Chung-Soo Kim, Young-Ah Suh, Se Jin Jang
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0119379 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25781604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histone Deacetylase Inhibitors
• Histones
• Hydroxamic Acids
• N1-(3-(dimethylamino)propyl)-N8-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide
• Naphthalenes
• RNA, Messenger

Topics

• Acetylation
• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Cycle (drug effects)
• Cell Differentiation
• Cell Proliferation (drug effects)
• Chromatin Immunoprecipitation
• Epigenomics
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Histones (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Lung Neoplasms (drug therapy, genetics, pathology)
• Naphthalenes (pharmacology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured