Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A

Actin plays a role in various processes in eukaryotic cells, including cell growth and death. We investigated whether the antitumor effect of trichostatin A (TSA) is associated with the dynamic rearrangement of F-actin. TSA is an antitumor drug that induces hyper-acetylation of histones by inhibitin...

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Autores principales: Yang, Dong-Hee, Lee, Jae-Wook, Lee, Jiyoung, Moon, Eun-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028200/
https://www.ncbi.nlm.nih.gov/pubmed/24846135
http://dx.doi.org/10.1371/journal.pone.0097352
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author Yang, Dong-Hee
Lee, Jae-Wook
Lee, Jiyoung
Moon, Eun-Yi
author_facet Yang, Dong-Hee
Lee, Jae-Wook
Lee, Jiyoung
Moon, Eun-Yi
author_sort Yang, Dong-Hee
collection PubMed
description Actin plays a role in various processes in eukaryotic cells, including cell growth and death. We investigated whether the antitumor effect of trichostatin A (TSA) is associated with the dynamic rearrangement of F-actin. TSA is an antitumor drug that induces hyper-acetylation of histones by inhibiting histone deacetylase. HeLa human cervical cancer cells were used to measure the antitumor effect of TSA. The percent cell survival was determined by an MTT assay. Hypodiploid cell formation was assessed by flow cytometry. Collapse of the mitochondrial membrane potential (MMP) was identified by a decrease in the percentage of cells with red MitoProbe J-aggregate (JC-1) fluorescence. Cell survival was reduced by treatment with TSA, as judged by an MTT assay and staining with propidium iodide, FITC-labeled annexin V, or 4′,6-diamidino-2-phenylindole (DAPI). TSA also induced an MMP collapse, as judged by the measurement of intracellular red JC-1 fluorescence. In addition, the F-actin depolymerizers cytochalasin D (CytoD) and latrunculin B (LatB) induced an MMP collapse and increased apoptotic cell death in HeLa cells. However, our data show that apoptotic cell death and the MMP collapse induced by TSA were decreased by the co-treatment of cells with CytoD and LatB. These findings demonstrate that the dynamic rearrangement of F-actin might be necessary for TSA-induced HeLa cell apoptosis involving a TSA-induced MMP collapse. They also suggest that actin cytoskeleton dynamics play an important role in maintaining the therapeutic effects of antitumor agents in tumor cells. They further suggest that maintaining the MMP could be a novel strategy for increasing drug sensitivity in TSA-treated tumors.
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spelling pubmed-40282002014-05-21 Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A Yang, Dong-Hee Lee, Jae-Wook Lee, Jiyoung Moon, Eun-Yi PLoS One Research Article Actin plays a role in various processes in eukaryotic cells, including cell growth and death. We investigated whether the antitumor effect of trichostatin A (TSA) is associated with the dynamic rearrangement of F-actin. TSA is an antitumor drug that induces hyper-acetylation of histones by inhibiting histone deacetylase. HeLa human cervical cancer cells were used to measure the antitumor effect of TSA. The percent cell survival was determined by an MTT assay. Hypodiploid cell formation was assessed by flow cytometry. Collapse of the mitochondrial membrane potential (MMP) was identified by a decrease in the percentage of cells with red MitoProbe J-aggregate (JC-1) fluorescence. Cell survival was reduced by treatment with TSA, as judged by an MTT assay and staining with propidium iodide, FITC-labeled annexin V, or 4′,6-diamidino-2-phenylindole (DAPI). TSA also induced an MMP collapse, as judged by the measurement of intracellular red JC-1 fluorescence. In addition, the F-actin depolymerizers cytochalasin D (CytoD) and latrunculin B (LatB) induced an MMP collapse and increased apoptotic cell death in HeLa cells. However, our data show that apoptotic cell death and the MMP collapse induced by TSA were decreased by the co-treatment of cells with CytoD and LatB. These findings demonstrate that the dynamic rearrangement of F-actin might be necessary for TSA-induced HeLa cell apoptosis involving a TSA-induced MMP collapse. They also suggest that actin cytoskeleton dynamics play an important role in maintaining the therapeutic effects of antitumor agents in tumor cells. They further suggest that maintaining the MMP could be a novel strategy for increasing drug sensitivity in TSA-treated tumors. Public Library of Science 2014-05-20 /pmc/articles/PMC4028200/ /pubmed/24846135 http://dx.doi.org/10.1371/journal.pone.0097352 Text en © 2014 Yang 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
Yang, Dong-Hee
Lee, Jae-Wook
Lee, Jiyoung
Moon, Eun-Yi
Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title_full Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title_fullStr Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title_full_unstemmed Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title_short Dynamic Rearrangement of F-Actin Is Required to Maintain the Antitumor Effect of Trichostatin A
title_sort dynamic rearrangement of f-actin is required to maintain the antitumor effect of trichostatin a
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028200/
https://www.ncbi.nlm.nih.gov/pubmed/24846135
http://dx.doi.org/10.1371/journal.pone.0097352
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