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

De U, Kundu S, Patra N, Ahn MY, Ahn JH, Son JY, Yoon JH, Moon HR, Lee BM, Kim HS - Biomol Ther (Seoul) (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746.

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.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of 5-hydroxy-7-(oxiran-2-ylmethoxy)-2-phenyl-4H-chromen-4-one (MHY219) and SAHA.
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f1-bt-23-434: Chemical structure of 5-hydroxy-7-(oxiran-2-ylmethoxy)-2-phenyl-4H-chromen-4-one (MHY219) and SAHA.

Mentions: In this study, we synthesized MHY219 as a novel HDAC inhibitor, a hydroxamic acid derivative, by incorporating one phenylamino group in position 4 of the phenyl ring of SAHA (Fig. 1). The effects of MHY219 on prostate cancer cell migration were investigated and compared with that of SAHA.


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

De U, Kundu S, Patra N, Ahn MY, Ahn JH, Son JY, Yoon JH, Moon HR, Lee BM, Kim HS - Biomol Ther (Seoul) (2015)

Chemical structure of 5-hydroxy-7-(oxiran-2-ylmethoxy)-2-phenyl-4H-chromen-4-one (MHY219) and SAHA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556203&req=5

f1-bt-23-434: Chemical structure of 5-hydroxy-7-(oxiran-2-ylmethoxy)-2-phenyl-4H-chromen-4-one (MHY219) and SAHA.
Mentions: In this study, we synthesized MHY219 as a novel HDAC inhibitor, a hydroxamic acid derivative, by incorporating one phenylamino group in position 4 of the phenyl ring of SAHA (Fig. 1). The effects of MHY219 on prostate cancer cell migration were investigated and compared with that of SAHA.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746.

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.

No MeSH data available.


Related in: MedlinePlus