A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1.
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.
School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
Umasankar
U
De
College of Pharmacy, Pusan National University, Busan 609-735.
Soma
S
Kundu
College of Pharmacy, Pusan National University, Busan 609-735.
Nabanita
N
Patra
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea.
Mee Young
MY
Ahn
School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
Ji Hae
JH
Ahn
School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
Ji Yeon
JY
Son
College of Pharmacy, Pusan National University, Busan 609-735.
Jung Hyun
JH
Yoon
College of Pharmacy, Pusan National University, Busan 609-735.
Hyung Ryoung
HR
Moon
School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
Byung Mu
BM
Lee
School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
Hyung Sik
HS
Kim
HDAC inhibitor; MHY219; MMPs; Migration; Prostate cancer