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

PloS One
Sung-Min ChunSe Jin Jang

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.

References

Oct 6, 2001·Cancer Chemotherapy and Pharmacology·M YoshidaS Horinouchi
Nov 14, 2002·The Biochemical Journal·Annemieke J M de RuijterAndré B P van Kuilenburg
Apr 8, 2003·Current Medicinal Chemistry. Anti-cancer Agents·G Kouraklis, S Theocharis
May 29, 2003·Current Medicinal Chemistry. Anti-cancer Agents·Wei-Guo Zhu, Gregory A Otterson
Apr 23, 2004·The EMBO Journal·Masayoshi YadaKeiichi I Nakayama
May 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Markus WelckerBruce E Clurman
Mar 2, 2005·Cell Cycle·Paul A Marks, Xuejun Jiang
Apr 12, 2005·European Journal of Cell Biology·Holger Hess-Stumpp
Nov 26, 2005·Expert Opinion on Investigational Drugs·Paul A Marks, Milos Dokmanovic
Sep 7, 2006·Nature Reviews. Drug Discovery·Jessica E BoldenRicky W Johnstone
Nov 30, 2006·Journal of Applied Genetics·Jaroslaw Paluszczak, Wanda Baer-Dubowska
Feb 28, 2007·Cell Research·Paola GallinariChristian Steinkühler
Mar 7, 2007·Nature Reviews. Genetics·Manel Esteller
Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elise A OlsenMadeleine Duvic
Oct 7, 2008·The International Journal of Biochemistry & Cell Biology·Jingde Zhu, Xuebiao Yao
Apr 10, 2009·Current Topics in Medicinal Chemistry·Ralf Ficner
May 22, 2009·Journal of Cellular Biochemistry·P A Marks, W-S Xu
Jun 8, 2012·Frontiers in Physiology·S D L Postnikoff, T A A Harkness

❮ Previous
Next ❯

Citations

Oct 29, 2015·Acta Biochimica Et Biophysica Sinica·Bo NingRongfu Wang
Sep 10, 2016·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Eunjo LeeInkyeom Kim
Jan 30, 2019·International Journal of Molecular Sciences·Eun Hui BaeSoo Wan Kim
Jan 1, 2016·Oncology and Therapy·Christopher R Heery
Nov 10, 2020·Frontiers in Cell and Developmental Biology·Hirva Mamdani, Shadia I Jalal
Dec 3, 2020·Frontiers in Oncology·Donglu WuDa Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
histone acetylation
acetylation
PCR
Flow cytometry
FACS
immunoprecipitation
ChIP
optical microscopy
xenograft
ubiquitination

Software Mentioned

Cell Quest
DAVID ( Database for Annotation , Visualization , and Integrat...
WorkOut

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Cancer Epigenetics and Chemical Tools (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Using novel chemical tools allows us to learn more about these epigenetic changes and how they impact the neoplastic process. Follow this feed to learn more about cancer epigenetics and chemical tools.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.