A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1

Biomolecules & Therapeutics
Umasankar DeHyung Sik Kim

Abstract

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP (IC50=0.67 μM) than in DU145 cells (IC50=1.10 μM) and PC3 cells (IC50=5.60 μM) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

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Citations

Jul 30, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lu-Hong LiZhi-Chao Li
May 31, 2016·Bioorganic Chemistry·Mohammed ManalM J Nanjan
Mar 10, 2017·Biomolecules & Therapeutics·June Hee KangChang Hoon Lee
Nov 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Santiago GarcíaMiguel A Vazquez
Mar 7, 2021·International Journal of Molecular Sciences·Simona De SummaAmalia Azzariti

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Methods Mentioned

BETA
histone acetylation
protein assay
PCR
electrophoresis

Software Mentioned

GraphPad Prism
SigmaPlot
GraphPad

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