Roles of Histone Deacetylases and Inhibitors in Anticancer Therapy

Autor(es)

Verza, Flavia Alves ^[1] ; Das, Umashankar ^[2] ; Fachin, Ana Lucia ^{[1, 3]} ; Dimmock, Jonathan R. ^[2] ; Marins, Mozart ^{[1, 3, 2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Ribeirao Preto, Biotechnol Unit, BR-14096900 Ribeirao Preto, SP - Brazil

^[2] Univ Saskatchewan, Coll Pharm & Nutr, 110 Sci Pl, Saskatoon, SK S7N 5C9 - Canada

^[3] Univ Ribeirao Preto, Med Sch, BR-14096900 Ribeirao Preto, SP - Brazil

^[4] Univ Ribeirao Preto, Pharmaceut Sci Sch, BR-14096900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: CANCERS; v. 12, n. 6 JUN 2020.
• Citações Web of Science: 0

Resumo

Histones are the main structural proteins of eukaryotic chromatin. Histone acetylation/ deacetylation are the epigenetic mechanisms of the regulation of gene expression and are catalyzed by histone acetyltransferases (HAT) and histone deacetylases (HDAC). These epigenetic alterations of DNA structure influence the action of transcription factors which can induce or repress gene transcription. The HATs catalyze acetylation and the events related to gene transcription and are also responsible for transporting newly synthesized histones from the cytoplasm to the nucleus. The activity of HDACs is mainly involved in silencing gene expression and according to their specialized functions are divided into classes I, II, III and IV. The disturbance of the expression and mutations of HDAC genes causes the aberrant transcription of key genes regulating important cancer pathways such as cell proliferation, cell-cycle regulation and apoptosis. In view of their role in cancer pathways, HDACs are considered promising therapeutic targets and the development of HDAC inhibitors is a hot topic in the search for new anticancer drugs. The present review will focus on HDACs I, II and IV, the best known inhibitors and potential alternative inhibitors derived from natural and synthetic products which can be used to influence HDAC activity and the development of new cancer therapies. (AU)

• Processo FAPESP: 18/50008-1 - Synthesis and discovery of molecular mechanisms of some novel conjugated unsaturated ketones designed as anticancer agents
• Beneficiário: Mozart de Azevedo Marins
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/03074-1 - Explorando a atividade do fator de transcrição Sp1 associada a transição epitélio mesenquimal como alvo terapêutico do osteossarcoma
• Beneficiário: Mozart de Azevedo Marins
• Linha de fomento: Auxílio à Pesquisa - Regular