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Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Korean Society of Environmental Health and Toxicology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355273/ https://www.ncbi.nlm.nih.gov/pubmed/22639737 http://dx.doi.org/10.5620/eht.2012.27.e2012010 |
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author | Min, Kyung Nan Joung, Ki Eun Kim, Dae-Kee Sheen, Yhun Yhong |
author_facet | Min, Kyung Nan Joung, Ki Eun Kim, Dae-Kee Sheen, Yhun Yhong |
author_sort | Min, Kyung Nan |
collection | PubMed |
description | 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 G(2)/M phase and of the sub-G(1) 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 p21(WAF1) 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. |
format | Online Article Text |
id | pubmed-3355273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Korean Society of Environmental Health and Toxicology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33552732012-05-25 Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer Min, Kyung Nan Joung, Ki Eun Kim, Dae-Kee Sheen, Yhun Yhong Environ Health Toxicol Original Article 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 G(2)/M phase and of the sub-G(1) 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 p21(WAF1) 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. The Korean Society of Environmental Health and Toxicology 2012-04-25 /pmc/articles/PMC3355273/ /pubmed/22639737 http://dx.doi.org/10.5620/eht.2012.27.e2012010 Text en © 2012 The Korean Society of Environmental Health and Toxicology http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Min, Kyung Nan Joung, Ki Eun Kim, Dae-Kee Sheen, Yhun Yhong Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title | Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title_full | Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title_fullStr | Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title_full_unstemmed | Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title_short | Anti-Cancer Effect of 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide in MCF-7 Human Breast Cancer |
title_sort | anti-cancer effect of 3-(4-dimethylamino phenyl)-n-hydroxy-2-propenamide in mcf-7 human breast cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355273/ https://www.ncbi.nlm.nih.gov/pubmed/22639737 http://dx.doi.org/10.5620/eht.2012.27.e2012010 |
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