Histone acetylation and cancer

doi:10.1016/S0959-437X(99)80026-4

Current Opinion in Genetics & Development

Volume 9, Issue 2, April 1999, Pages 171-174

https://doi.org/10.1016/S0959-437X(99)80026-4 Get rights and content

In the past year, several papers have been published which implicate a link between alterations in chromatin structure and the development of cancer. Both histone hyperacetylation and hypoacetylation appear to be important in the neoplastic process, depending on the target gene involved. In the case of colon cancer, induction of the p21 gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis.

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Based on fragment-based virtual screening and bioisoterism strategies, novel indazole and pyrazolo[3,4-b] pyridine derivatives as HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDACs, especially compounds 15k and 15m were identified as potent inhibitors of HDAC1 (IC₅₀ = 2.7 nM and IC₅₀ = 3.1 nM), HDAC2 (IC₅₀ = 4.2 nM and IC₅₀ = 3.6 nM) and HDAC8 (IC₅₀ = 3.6 nM and IC₅₀ = 3.3 nM). Further anti-proliferation assays revealed that compounds 15k and 15m showed better anti-proliferative activities against HCT-116 and HeLa cells than positive control SAHA. The western blot analysis results indicated that compounds 15k and 15m noticeably up-regulated the level of acetylated α-tubulin and histone H3. In addition, the two compounds 15k and 15m could arrest cell cycle in G2/M phase and promote cell apoptosis, which was similar as the reference compound SAHA. Through the molecular docking and dynamic studies, the potent HDAC inhibitory activities mainly caused by van der Waals and electrostatic interactions with the HDACs.
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This chapter covers the broad field of transcription and epigenetic regulatory mechanisms to equip the gastrointestinal physiologist with the tools to understand gene expression. This chapter reviews the composition of the nucleic acids and the methods used to study their structure and function. The effect of noncoding RNA species such as microRNA and long noncoding RNAs is discussed. In addition, the impact of histone and DNA modification on gene expression collectively known as epigenetic influences are discussed in the context of how the gut microenvironment.

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Histone acetylation and cancer

Trends Gene

Nature

Gastroenterology

Surgery

Carcinogenesis

Cancer Res

Exp Cell Res

J Biol Chem

Analysis of subunit organization in chicken erythrocyte chromatin

Histone acetylation in chromatin structure and transcription

Nature

Histone acetylation and transcriptional regulatory mechanisms

Genes Dev

Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression

Nature

Histone deacetylase activity is required for full transcriptional repression by mSin3

Cell

Retinoblastoma protein recruits histone deacetylase to repress transcription

Nature

Retinoblastoma protein represses transcription by recruiting a histone deacetylase

Nature

Histone acetylation decreased by estradiol in the MCF-7 human mammary cancer cell line

Breast Cancer Res Treat