A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1.
10.4062/biomolther.2015.026
- Author:
Umasankar DE
1
;
Soma KUNDU
;
Nabanita PATRA
;
Mee Young AHN
;
Ji Hae AHN
;
Ji Yeon SON
;
Jung Hyun YOON
;
Hyung Ryoung MOON
;
Byung Mu LEE
;
Hyung Sik KIM
Author Information
1. School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. hkims@skku.edu
- Publication Type:Original Article
- Keywords:
HDAC inhibitor;
MHY219;
MMPs;
Migration;
Prostate cancer
- MeSH:
Cell Movement;
Down-Regulation;
Drug Therapy;
Histone Deacetylase Inhibitors*;
Histone Deacetylases*;
Histones*;
Humans*;
Matrix Metalloproteinases;
Prostate*;
Prostatic Neoplasms*;
Repression, Psychology
- From:Biomolecules & Therapeutics
2015;23(5):434-441
- CountryRepublic of Korea
- Language:English
-
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 muM) than in DU145 cells (IC50=1.10 muM) and PC3 cells (IC50=5.60 muM) 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.
