Environ Health Toxicol.  2012 ;27(1):e2012010.

Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer

• Min KN
• Joung KE
• Kim DK
• Sheen YY

Abstract

OBJECTIVES
In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the anti-tumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells.
METHODS
We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR.
RESULTS
In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at G2/M phase and of the sub-G1 population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased p21WAF1 expression.
CONCLUSIONS
In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

Keyword

Histone deacetylase; 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide; MCF-7; Breast cancer

MeSH Terms

Amides
Apoptosis
Apoptosis Regulatory Proteins
Breast
Breast Neoplasms
Cell Cycle
Cell Cycle Checkpoints
Cell Proliferation
Cyclins
Estrogens
Flow Cytometry
Gene Expression
Histone Deacetylase Inhibitors
Histone Deacetylases
Humans
Hydroxamic Acids
MCF-7 Cells
Phosphotransferases
Propane
Amides
Apoptosis Regulatory Proteins
Cyclins
Estrogens
Histone Deacetylase Inhibitors
Histone Deacetylases
Hydroxamic Acids
Phosphotransferases
Propane