Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy.

Autor: Ramaiah MJ; Laboratory of Functional genomics and Disease Biology, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India. Electronic address: janakiramaiah@scbt.sastra.edu., Tangutur AD; Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500 007, Telangana, India., Manyam RR; Department of Computer Science and Engineering, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Andhra Pradesh, India.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Jul 15; Vol. 277, pp. 119504. Date of Electronic Publication: 2021 Apr 16.
DOI: 10.1016/j.lfs.2021.119504
Abstrakt: The role of genetic and epigenetic factors in tumor initiation and progression is well documented. Histone deacetylases (HDACs), histone methyl transferases (HMTs), and DNA methyl transferases. (DNMTs) are the main proteins that are involved in regulating the chromatin conformation. Among these, histone deacetylases (HDAC) deacetylate the histone and induce gene repression thereby leading to cancer. In contrast, histone acetyl transferases (HATs) that include GCN5, p300/CBP, PCAF, Tip 60 acetylate the histones. HDAC inhibitors are potent drug molecules that can induce acetylation of histones at lysine residues and induce open chromatin conformation at tumor suppressor gene loci and thus resulting in tumor suppression. The key processes regulated by HDAC inhibitors include cell-cycle arrest, chemo-sensitization, apoptosis induction, upregulation of tumor suppressors. Even though FDA approved drugs are confined mainly to haematological malignancies, the research on HDAC inhibitors in glioblastoma multiforme and triple negative breast cancer (TNBC) are providing positive results. Thus, several combinations of HDAC inhibitors along with DNA methyl transferase inhibitors and histone methyl transferase inhibitors are in clinical trials. This review focuses on how HDAC inhibitors regulate the expression of coding and non-coding genes with specific emphasis on their anti-cancer potential.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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