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

Chun SM, Lee JY, Choi J, Lee JH, Hwang JJ, Kim CS, Suh YA, Jang SJ - PLoS ONE (2015)

Bottom Line: Histone modification plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Flow cytometric investigations of CG200745-treated Calu6 cells.Calu6 cells treated with 3 μM of CG200745 were analyzed cell cycles on flow cytometer. Each histogram consists of two black peaks and one scratched region indicating G0/G1 phase, G2/M phase, and S phase, respectively. The effect of CG200745 on the cell cycle distribution was analyzed at for various time points (A), or compared to untreated cells (B) depicting as a graphical view (C).
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pone.0119379.g002: Flow cytometric investigations of CG200745-treated Calu6 cells.Calu6 cells treated with 3 μM of CG200745 were analyzed cell cycles on flow cytometer. Each histogram consists of two black peaks and one scratched region indicating G0/G1 phase, G2/M phase, and S phase, respectively. The effect of CG200745 on the cell cycle distribution was analyzed at for various time points (A), or compared to untreated cells (B) depicting as a graphical view (C).

Mentions: HDACi compounds are known to induce cell cycle arrest, an important cancer target mechanism, in various cancer cells. To examine whether CG200745 induced cycle arrest in the Calu6 cell line, these cells were treated with this HDACi molecule for various time points from 0 to 24 hours, followed by flow cytometric analysis (FACS). As shown in Fig. 2A, an increase in the G2/M population was observed in a time-dependent manner. CG200745-treated Calu6 cells showed a significantly increased cell proportion in G2/M phase (69%) compared to untreated control cells (26%) (Figs. 2B and 2C). These results indicate that CG200745 causes cell growth inhibition through G2/M phase cell cycle arrest.


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

Chun SM, Lee JY, Choi J, Lee JH, Hwang JJ, Kim CS, Suh YA, Jang SJ - PLoS ONE (2015)

Flow cytometric investigations of CG200745-treated Calu6 cells.Calu6 cells treated with 3 μM of CG200745 were analyzed cell cycles on flow cytometer. Each histogram consists of two black peaks and one scratched region indicating G0/G1 phase, G2/M phase, and S phase, respectively. The effect of CG200745 on the cell cycle distribution was analyzed at for various time points (A), or compared to untreated cells (B) depicting as a graphical view (C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363698&req=5

pone.0119379.g002: Flow cytometric investigations of CG200745-treated Calu6 cells.Calu6 cells treated with 3 μM of CG200745 were analyzed cell cycles on flow cytometer. Each histogram consists of two black peaks and one scratched region indicating G0/G1 phase, G2/M phase, and S phase, respectively. The effect of CG200745 on the cell cycle distribution was analyzed at for various time points (A), or compared to untreated cells (B) depicting as a graphical view (C).
Mentions: HDACi compounds are known to induce cell cycle arrest, an important cancer target mechanism, in various cancer cells. To examine whether CG200745 induced cycle arrest in the Calu6 cell line, these cells were treated with this HDACi molecule for various time points from 0 to 24 hours, followed by flow cytometric analysis (FACS). As shown in Fig. 2A, an increase in the G2/M population was observed in a time-dependent manner. CG200745-treated Calu6 cells showed a significantly increased cell proportion in G2/M phase (69%) compared to untreated control cells (26%) (Figs. 2B and 2C). These results indicate that CG200745 causes cell growth inhibition through G2/M phase cell cycle arrest.

Bottom Line: Histone modification plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Asan Medical Center, The University of Ulsan College of Medicine, Seoul, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus