Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based inhibitors of histone deacetylases

• 4-HBA derivatives inhibit HDAC activities and lead to increased protein acetylation.
• 4-HBA derivatives display anti-tumor activities against solid and non-solid cancer cells.
• Cancer cells are more sensitive to 4-HBA treatments than normal cells.

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.