Anticancer Effect of a Novel Histone Deacetylase Inhibitor in Cell Model

Abstract

Histone deacetylases (HDACs) are potential therapeutic targets for the treatment of hematologic and solid tumor malignancies due to their overexpression and/or increased activity in various cancers. Although HDAC inhibitors exhibit significant inhibition ability in hematological cancers, their effect in solid tumors has not been satisfactory. Here, we propose a novel HDAC inhibitor, N-hydroxy-4-((1R,2R)- 2-phenylcyclopropanecarboxamido)benzamide (HPCPCB), as a chemotherapeutic drug for solid tumors. First, we examined the cytotoxicity of HPCPCB in various lung and breast cancer cells and their corresponding normal cells using MTT assay. HPCPCB showed significant growth inhibition on various cancer cells, while there was no serious cytotoxicity against normal cells. Results of flow cytometry showed that HPCPCB caused cell cycle arrest at G1 phase. Western blotting indicated that proteins required for cell cycle progression such as CDC25A, CDK4 and cyclin E were reduced and the cell cycle inhibitor p21 was up-regulated by HPCPCB treatment. Furthermore, HPCPCB inhibited HDAC activity and induced an increase in acetylated histone proteins H3 and H4 and non-histone proteins p53 and tubulin. Our findings suggest that HPCPCB is a potent HDAC inhibitor and has potential in cancer treatment.