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Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer
Environmental Health and Toxicology ; : e2012010-2012.
Artigo em Inglês | WPRIM | ID: wpr-118825
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fosfotransferases / Propano / Mama / Neoplasias da Mama / Expressão Gênica / Ciclo Celular / Apoptose / Ciclinas / Proliferação de Células / Estrogênios Tipo de estudo: Estudo prognóstico Limite: Humanos Idioma: Inglês Revista: Environmental Health and Toxicology Ano de publicação: 2012 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fosfotransferases / Propano / Mama / Neoplasias da Mama / Expressão Gênica / Ciclo Celular / Apoptose / Ciclinas / Proliferação de Células / Estrogênios Tipo de estudo: Estudo prognóstico Limite: Humanos Idioma: Inglês Revista: Environmental Health and Toxicology Ano de publicação: 2012 Tipo de documento: Artigo