Cargando…
Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line
Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA) in combination with arsenic trioxide (ATO) on proliferation and apoptosis of K562 cells. Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexi...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451029/ https://www.ncbi.nlm.nih.gov/pubmed/26038719 http://dx.doi.org/10.7717/peerj.962 |
_version_ | 1782374087819001856 |
---|---|
author | Li, Nainong Guan, Xiaoyan Li, Fang Li, Xiaofan Chen, Yuanzhong |
author_facet | Li, Nainong Guan, Xiaoyan Li, Fang Li, Xiaofan Chen, Yuanzhong |
author_sort | Li, Nainong |
collection | PubMed |
description | Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA) in combination with arsenic trioxide (ATO) on proliferation and apoptosis of K562 cells. Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexin-V and PI staining by flow cytometry and acridine orange/ethidium bromide stains were used to detect and quantify apoptosis. Western blot was used to detect expression of p21, Akt, pAkt, p210, Acetyl-Histone H3, and Acetyl-Histone H4 proteins. Results. SAHA and ATO inhibited proliferation of K562 cells in an additive and time- and dose-dependent manner. SAHA in combination with ATO showed significant apoptosis of K562 cells in comparison to the single drugs alone (p < 0.01). Both SAHA and ATO alone and in combination showed lower levels of p210 expression. SAHA and SAHA and ATO combined treatment showed increased levels of Acetyl-Histone H3 and Acetyl-Histone H4 protein expression. SAHA alone showed increased expression of p21, while ATO alone and in combination with SAHA showed no significant change. SAHA and ATO combined therapy showed lower levels of Akt and pAkt protein expression than SAHA or ATO alone. Conclusion. SAHA and ATO combined treatment inhibited proliferation, induced apoptosis, and showed a chemosensitive augmentation effect on K562 cells. The mechanism might be associated with increasing histone acetylation levels as well as regulating the Akt signaling pathway. |
format | Online Article Text |
id | pubmed-4451029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44510292015-06-02 Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line Li, Nainong Guan, Xiaoyan Li, Fang Li, Xiaofan Chen, Yuanzhong PeerJ Cell Biology Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA) in combination with arsenic trioxide (ATO) on proliferation and apoptosis of K562 cells. Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexin-V and PI staining by flow cytometry and acridine orange/ethidium bromide stains were used to detect and quantify apoptosis. Western blot was used to detect expression of p21, Akt, pAkt, p210, Acetyl-Histone H3, and Acetyl-Histone H4 proteins. Results. SAHA and ATO inhibited proliferation of K562 cells in an additive and time- and dose-dependent manner. SAHA in combination with ATO showed significant apoptosis of K562 cells in comparison to the single drugs alone (p < 0.01). Both SAHA and ATO alone and in combination showed lower levels of p210 expression. SAHA and SAHA and ATO combined treatment showed increased levels of Acetyl-Histone H3 and Acetyl-Histone H4 protein expression. SAHA alone showed increased expression of p21, while ATO alone and in combination with SAHA showed no significant change. SAHA and ATO combined therapy showed lower levels of Akt and pAkt protein expression than SAHA or ATO alone. Conclusion. SAHA and ATO combined treatment inhibited proliferation, induced apoptosis, and showed a chemosensitive augmentation effect on K562 cells. The mechanism might be associated with increasing histone acetylation levels as well as regulating the Akt signaling pathway. PeerJ Inc. 2015-05-28 /pmc/articles/PMC4451029/ /pubmed/26038719 http://dx.doi.org/10.7717/peerj.962 Text en © 2015 Li 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Cell Biology Li, Nainong Guan, Xiaoyan Li, Fang Li, Xiaofan Chen, Yuanzhong Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title | Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title_full | Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title_fullStr | Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title_full_unstemmed | Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title_short | Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line |
title_sort | vorinostat enhances chemosensitivity to arsenic trioxide in k562 cell line |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451029/ https://www.ncbi.nlm.nih.gov/pubmed/26038719 http://dx.doi.org/10.7717/peerj.962 |
work_keys_str_mv | AT linainong vorinostatenhanceschemosensitivitytoarsenictrioxideink562cellline AT guanxiaoyan vorinostatenhanceschemosensitivitytoarsenictrioxideink562cellline AT lifang vorinostatenhanceschemosensitivitytoarsenictrioxideink562cellline AT lixiaofan vorinostatenhanceschemosensitivitytoarsenictrioxideink562cellline AT chenyuanzhong vorinostatenhanceschemosensitivitytoarsenictrioxideink562cellline |