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Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids

Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibi...

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Autores principales: Han, Shaoteng, Fukazawa, Takuya, Yamatsuji, Tomoki, Matsuoka, Junji, Miyachi, Hiroyuki, Maeda, Yutaka, Durbin, Mary, Naomoto, Yoshio
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973950/
https://www.ncbi.nlm.nih.gov/pubmed/21079797
http://dx.doi.org/10.1371/journal.pone.0013834
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author Han, Shaoteng
Fukazawa, Takuya
Yamatsuji, Tomoki
Matsuoka, Junji
Miyachi, Hiroyuki
Maeda, Yutaka
Durbin, Mary
Naomoto, Yoshio
author_facet Han, Shaoteng
Fukazawa, Takuya
Yamatsuji, Tomoki
Matsuoka, Junji
Miyachi, Hiroyuki
Maeda, Yutaka
Durbin, Mary
Naomoto, Yoshio
author_sort Han, Shaoteng
collection PubMed
description Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARα, RARβ, RXRα and RXRβ were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer.
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spelling pubmed-29739502010-11-15 Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids Han, Shaoteng Fukazawa, Takuya Yamatsuji, Tomoki Matsuoka, Junji Miyachi, Hiroyuki Maeda, Yutaka Durbin, Mary Naomoto, Yoshio PLoS One Research Article Histone deacetylase (HDAC) inhibitors arrest cancer cell growth and cause apoptosis with low toxicity thereby constituting a promising treatment for cancer. In this study, we investigated the anti-tumor activity in lung cancer cells of the novel cyclic amide-bearing hydroxamic acid based HDAC inhibitors SL142 and SL325. In A549 and H441 lung cancer cells both SL142 and SL325 induced more cell growth inhibition and cell death than the hydroxamic acid-based HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Moreover, the combination treatment using retinoid drugs ATRA or 9-cis RA along with SL142 or SL325 significantly induced more apoptosis and suppressed colony formation than the single use of either. The expression of the retinoic acid receptors RARα, RARβ, RXRα and RXRβ were unchanged with the treatment. However a luciferase reporter construct (pGL4. RARE 7x) containing seven tandem repeats of the retinoic acid responsible element (RARE) generated significant transcriptional activity after the combination treatment of retinoic acids and SL142 or SL325 in H441 lung cancer cells. Moreover, apoptosis-promoting Bax expression and caspase-3 activity was increased after the combination treatment. These results suggest that the combination treatment of SL142 or SL325 with retinoic acids exerts significant anti-tumor activity and is a promising therapeutic candidate to treat human lung cancer. Public Library of Science 2010-11-04 /pmc/articles/PMC2973950/ /pubmed/21079797 http://dx.doi.org/10.1371/journal.pone.0013834 Text en Han et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Han, Shaoteng
Fukazawa, Takuya
Yamatsuji, Tomoki
Matsuoka, Junji
Miyachi, Hiroyuki
Maeda, Yutaka
Durbin, Mary
Naomoto, Yoshio
Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title_full Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title_fullStr Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title_full_unstemmed Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title_short Anti-Tumor Effect in Human Lung Cancer by a Combination Treatment of Novel Histone Deacetylase Inhibitors: SL142 or SL325 and Retinoic Acids
title_sort anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: sl142 or sl325 and retinoic acids
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973950/
https://www.ncbi.nlm.nih.gov/pubmed/21079797
http://dx.doi.org/10.1371/journal.pone.0013834
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