HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases

Abstract

Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states. HDAC inhibitors have been highlighted as a novel category of anti-cancer drugs. To date, four HDAC inhibitors, Vorinostat, Romidepsin, Panobinostat, and Belinostat, have been approved by the United States Food and Drug Administration. Principally, these HDAC inhibitors are used for hematologic cancers in clinic with less severe side effects. Clinical trials are continuously expanding to address other types of cancer and also nonmalignant diseases. HDAC inhibition also results in beneficial outcomes in various types of neurodegenerative diseases, inflammation disorders, and cardiovascular diseases. In this review, we will briefly discuss 1) the roles of HDACs in the acquisition of a cancer's phenotype and the general outcome of the HDAC inhibitors in cancer, 2) the functional relevance of HDACs in cardiovascular diseases and the possible therapeutic implications of HDAC inhibitors in cardiovascular disease.

Timing and Targeting of Treatment in Left Ventricular Hypertrophy

“…Both HAT and HDAC inhibitors are being tested for control of cancer cells in clinical trials, but they have also been shown to play a role in controlling cardiac hypertrophy in animal models. 26,27 The evidence that inhibiting both global activators and repressors has beneficial effects in cardiac stress strongly supports the hypothesis that control of transcription flexibility, and not the exact gene expression per se, may be an effective therapy to manage already progressing cardiac stress.…”

Suberanilohydroxamic Acid as a Pharmacological Kruppel‐Like Factor 2 Activator That Represses Vascular Inflammation and Atherosclerosis

“…Preclinical atherosclerosis models have suggested that drugs modulating histone acetylation may be utilized to treat cardiovascular disease in the future 52. It is noteworthy that, to date, there are some debates on the effects of HDAC inhibitors in treating experimental atherosclerosis 50. Moreover, the side effects of HDAC inhibitor on the vascular system need to be systematically and closely monitored 50.…”

HTP Nutraceutical Screening for Histone Deacetylase Inhibitors and Effects of HDACis on Tumor-suppressing miRNAs by Trichostatin A and Grapeseed (Vitis vinifera) in HeLa cells

“…HDAC inhibitors are becoming a well-known class of drugs for cancer treatment, in particular after the FDA approval of Vorinostat and Romidepsin for the treatment of hematologic cancers (2). At least 12 different HDACis are currently in use for clinical trials, and more are being sought to augment chemotherapy (4, 5, 7), immunotherapy/ cancer vaccines (14) and overcome multi-drug resistance which are common to diverse cytostatic or receptor-mediated drugs (3,8,9,(36)(37)(38) HDAC inhibitors were first isolated from microorganisms, and continue to be developed from microbial metabolites (39,40).…”

“…Elevated expression of HDACs are evident in advanced malignancy, where inhibitors (HDACis) antagonize tumor growth (2,3) antagonize tumor growth (2,3), augment chemotherapy (4-7), reverse chemoresistance (3,8,9), attenuate metastasis, halt epithelial-mesenchymal transition (10)(11)(12) and block tumor immune evasion (13,14). With the overwhelming surge of HDACis being sought worldwide for nearly every type of cancer (e.g.…”