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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

Effect of MHY219 and SAHA on cell viability measured by MTT assay. (A) DU145 cells, (B) LNCaP cells, and (C) PC3 cells were treated with MHY219 and SAHA at various concentrations (0.01–10 μM/mL for 48 h. The percentage of viable cells was determined as the ratio between treated cells and untreated controls. Results were expressed as mean ± standard deviation (S.D.) of three independent experiments. *p<0.05 as determined by a Student t-test compared to the untreated control.
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f3-bt-23-434: Effect of MHY219 and SAHA on cell viability measured by MTT assay. (A) DU145 cells, (B) LNCaP cells, and (C) PC3 cells were treated with MHY219 and SAHA at various concentrations (0.01–10 μM/mL for 48 h. The percentage of viable cells was determined as the ratio between treated cells and untreated controls. Results were expressed as mean ± standard deviation (S.D.) of three independent experiments. *p<0.05 as determined by a Student t-test compared to the untreated control.

Mentions: MHY219 and SAHA significantly reduced the growth of human prostate cancer cells in a concentration- or time-dependent manner, as assessed by MTT assay (Fig. 3). MHY219 showed a more potent cytotoxic activity than SAHA against LNCaP, DU145, and PC3 cells with IC50 values of 3.98, 2.6, and >5 μM at 24 h and 0.97, 0.36, and 5.12 μM at 48 h, respectively. MHY219 and SAHA exhibited different sensitivity against the three prostate cancer cells lines. MHY219 and SAHA cytotoxicity was high in DU145 cells as compared to that in LNCaP and PC-3 cells.


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)

Effect of MHY219 and SAHA on cell viability measured by MTT assay. (A) DU145 cells, (B) LNCaP cells, and (C) PC3 cells were treated with MHY219 and SAHA at various concentrations (0.01–10 μM/mL for 48 h. The percentage of viable cells was determined as the ratio between treated cells and untreated controls. Results were expressed as mean ± standard deviation (S.D.) of three independent experiments. *p<0.05 as determined by a Student t-test compared to the untreated control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-bt-23-434: Effect of MHY219 and SAHA on cell viability measured by MTT assay. (A) DU145 cells, (B) LNCaP cells, and (C) PC3 cells were treated with MHY219 and SAHA at various concentrations (0.01–10 μM/mL for 48 h. The percentage of viable cells was determined as the ratio between treated cells and untreated controls. Results were expressed as mean ± standard deviation (S.D.) of three independent experiments. *p<0.05 as determined by a Student t-test compared to the untreated control.
Mentions: MHY219 and SAHA significantly reduced the growth of human prostate cancer cells in a concentration- or time-dependent manner, as assessed by MTT assay (Fig. 3). MHY219 showed a more potent cytotoxic activity than SAHA against LNCaP, DU145, and PC3 cells with IC50 values of 3.98, 2.6, and >5 μM at 24 h and 0.97, 0.36, and 5.12 μM at 48 h, respectively. MHY219 and SAHA exhibited different sensitivity against the three prostate cancer cells lines. MHY219 and SAHA cytotoxicity was high in DU145 cells as compared to that in LNCaP and PC-3 cells.

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