title: Understanding histone deacetylases in the cancer development and treatment: an epigenetic perspective of cancer chemotherapy.
abstract: Cancer is a pathologic condition that involves genetic and epigenetic events culminating in neoplastic transformation. Alteration in epigenetic events that regulate the transcriptional activity of genes associated with various signaling pathways can influence multiple stages of tumorigenesis. In cancer cells, an imbalance often exists between histone acetyl transferase and histone deacetylase (HDAC) activities, and current research focuses actively on seeking competitive HDAC inhibitors (HDACi) for chemotherapeutic intervention. HDACi are proving useful for cancer prevention and therapy by virtue of their ability to reactivate the expression of epigenetically silenced genes, including those involved in differentiation, cell cycle regulation, apoptosis, angiogenesis, invasion, and metastasis. Furthermore, epidemiological studies suggest that different diets such as intake of cruciferous vegetables may lower the risk of different cancers, and there is growing interest in identifying the specific chemoprotective constituents and mechanistic insights of their action. Interestingly, it has been observed that cancer cells are more sensitive than nontransformed cells to apoptotic induction by some HDACi. Although the mechanistic basis for this sensitivity is unclear, yet HDACi have emerged as important epigenetic target for single and combinatorial chemotherapy. HDACi derived from diverse sources such as microbial, dietary, and synthetic increase acetylation level of cells and bring about anti-proliferative and apoptotic effects specific to cancer cells by way of their role in cell cycle regulation and expression of epigenetically silenced genes.
authors.affiliation: Cancer Pharmacology Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu, India.
authors.forename: Mudassier
authors.initials: M
authors.lastname: Ahmad
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
authors.forename: Aashiq
authors.initials: A
authors.lastname: Hussain
authors.forename: Rabiya
authors.initials: R
authors.lastname: Majeed
authors.forename: Yasrib
authors.initials: Y
authors.lastname: Qurishi
authors.forename: Javeed Ahmad
authors.initials: JA
authors.lastname: Bhat
authors.forename: Rauf Ahmad
authors.initials: RA
authors.lastname: Najar
authors.forename: Asif Khurshid
authors.initials: AK
authors.lastname: Qazi
authors.forename: Mohmmad Afzal
authors.initials: MA
authors.lastname: Zargar
authors.forename: Shashank Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D000107:Acetylation / Q000187:drug effects; D004358:Drug Therapy / Q000379:methods / Q000639:trends; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases