Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases.
Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate cellular processes by modifying the acetylation status of many proteins. Pathologically altered HDAC activity contributes to cancer development and thus characterization of novel acetylation modulators is important for future anti-cancer therapies. In this study, we identified three novel 4-hydroxybenzoic acid derivatives as pan-HDAC inhibitors that increased protein acetylation levels, arrested cell cycle progression and triggered apoptotic cell death, without affecting viability of normal cells. Our data support the potential of 4-hydroxybenzoic acid derivatives as pan-HDAC inhibitors with anticancer properties.
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Carole
C
Seidel
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Michael
M
Schnekenburger
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Mario
M
Dicato
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg; Department of Pharmacy, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: marcdiederich@snu.ac.kr.
Marc
M
Diederich
D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D061986:MCF-7 Cells; D008938:Mitosis; D010226:Parabens / Q000737:chemistry*; D020298:U937 Cells
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D010226:Parabens; D006655:Histone Deacetylases; C038193:4-hydroxybenzoic acid
Acetylation; Apoptosis; Cancer; Cell cycle arrest; HDAC inhibitor; Leukemia