Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1

  • De, Umasankar (School of Pharmacy, Sungkyunkwan University) ;
  • Kundu, Soma (College of Pharmacy, Pusan National University) ;
  • Patra, Nabanita (College of Pharmacy, Pusan National University) ;
  • Ahn, Mee Young (Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Institute, Daejeon Dental Hospital, Wonkwang University) ;
  • Ahn, Ji Hae (School of Pharmacy, Sungkyunkwan University) ;
  • Son, Ji Yeon (School of Pharmacy, Sungkyunkwan University) ;
  • Yoon, Jung Hyun (College of Pharmacy, Pusan National University) ;
  • Moon, Hyung Ryoung (College of Pharmacy, Pusan National University) ;
  • Lee, Byung Mu (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Hyung Sik (School of Pharmacy, Sungkyunkwan University)
  • Received : 2015.03.09
  • Accepted : 2015.05.06
  • Published : 2015.09.01
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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 ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) 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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References

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