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Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells
In the present study we show that histone deacetylase inhibitors (HDACIs) enhance the anti-tumor effects of melanoma differentiation associated gene-7/interleukin 24 (mda-7/IL-24) in human renal carcinoma cells. Similar data were obtained in other GU tumor cells. Combination of these two agents resu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925659/ https://www.ncbi.nlm.nih.gov/pubmed/24025359 http://dx.doi.org/10.4161/cbt.26110 |
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author | Hamed, Hossein A Das, Swadesh K Sokhi, Upneet K Park, Margaret A Cruickshanks, Nichola Archer, Kellie Ogretmen, Besim Grant, Steven Sarkar, Devanand Fisher, Paul B Dent, Paul |
author_facet | Hamed, Hossein A Das, Swadesh K Sokhi, Upneet K Park, Margaret A Cruickshanks, Nichola Archer, Kellie Ogretmen, Besim Grant, Steven Sarkar, Devanand Fisher, Paul B Dent, Paul |
author_sort | Hamed, Hossein A |
collection | PubMed |
description | In the present study we show that histone deacetylase inhibitors (HDACIs) enhance the anti-tumor effects of melanoma differentiation associated gene-7/interleukin 24 (mda-7/IL-24) in human renal carcinoma cells. Similar data were obtained in other GU tumor cells. Combination of these two agents resulted in increased autophagy that was dependent on expression of ceramide synthase 6, with HDACIs enhancing MDA-7/IL-24 toxicity by increasing generation of ROS and Ca(2+). Knock down of CD95 protected cells from HDACI and MDA-7/IL-24 lethality. Sorafenib treatment further enhanced (HDACI + MDA-7/IL-24) lethality. Anoikis resistant renal carcinoma cells were more sensitive to MDA-7/IL-24 that correlated with elevated SRC activity and tyrosine phosphorylation of CD95. We employed a recently constructed serotype 5/3 adenovirus, which is more effective than a serotype 5 virus in delivering mda-7/IL-24 to renal carcinoma cells and which conditionally replicates (CR) in tumor cells expressing MDA-7/IL-24 by virtue of placing the adenoviral E1A gene under the control of the cancer-specific promoter progression elevated gene-3 (Ad.5/3-PEG-E1A-mda-7; CRAd.5/3-mda-7, Ad.5/3-CTV), to define efficacy in renal carcinoma cells. Ad.5/3-CTV decreased the growth of renal carcinoma tumors to a significantly greater extent than did a non-replicative virus Ad.5/3-mda-7. In contralateral uninfected renal carcinoma tumors Ad.5/3-CTV also decreased the growth of tumors to a greater extent than did Ad.5/3-mda-7. In summation, our data demonstrates that HDACIs enhance MDA-7/IL-24-mediated toxicity and tumor specific adenoviral delivery and viral replication of mda-7/IL-24 is an effective pre-clinical renal carcinoma therapeutic. |
format | Online Article Text |
id | pubmed-3925659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-39256592014-02-25 Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells Hamed, Hossein A Das, Swadesh K Sokhi, Upneet K Park, Margaret A Cruickshanks, Nichola Archer, Kellie Ogretmen, Besim Grant, Steven Sarkar, Devanand Fisher, Paul B Dent, Paul Cancer Biol Ther Research Paper In the present study we show that histone deacetylase inhibitors (HDACIs) enhance the anti-tumor effects of melanoma differentiation associated gene-7/interleukin 24 (mda-7/IL-24) in human renal carcinoma cells. Similar data were obtained in other GU tumor cells. Combination of these two agents resulted in increased autophagy that was dependent on expression of ceramide synthase 6, with HDACIs enhancing MDA-7/IL-24 toxicity by increasing generation of ROS and Ca(2+). Knock down of CD95 protected cells from HDACI and MDA-7/IL-24 lethality. Sorafenib treatment further enhanced (HDACI + MDA-7/IL-24) lethality. Anoikis resistant renal carcinoma cells were more sensitive to MDA-7/IL-24 that correlated with elevated SRC activity and tyrosine phosphorylation of CD95. We employed a recently constructed serotype 5/3 adenovirus, which is more effective than a serotype 5 virus in delivering mda-7/IL-24 to renal carcinoma cells and which conditionally replicates (CR) in tumor cells expressing MDA-7/IL-24 by virtue of placing the adenoviral E1A gene under the control of the cancer-specific promoter progression elevated gene-3 (Ad.5/3-PEG-E1A-mda-7; CRAd.5/3-mda-7, Ad.5/3-CTV), to define efficacy in renal carcinoma cells. Ad.5/3-CTV decreased the growth of renal carcinoma tumors to a significantly greater extent than did a non-replicative virus Ad.5/3-mda-7. In contralateral uninfected renal carcinoma tumors Ad.5/3-CTV also decreased the growth of tumors to a greater extent than did Ad.5/3-mda-7. In summation, our data demonstrates that HDACIs enhance MDA-7/IL-24-mediated toxicity and tumor specific adenoviral delivery and viral replication of mda-7/IL-24 is an effective pre-clinical renal carcinoma therapeutic. Landes Bioscience 2013-11-01 2013-08-28 /pmc/articles/PMC3925659/ /pubmed/24025359 http://dx.doi.org/10.4161/cbt.26110 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Research Paper Hamed, Hossein A Das, Swadesh K Sokhi, Upneet K Park, Margaret A Cruickshanks, Nichola Archer, Kellie Ogretmen, Besim Grant, Steven Sarkar, Devanand Fisher, Paul B Dent, Paul Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title | Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title_full | Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title_fullStr | Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title_full_unstemmed | Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title_short | Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells |
title_sort | combining histone deacetylase inhibitors with mda-7/il-24 enhances killing of renal carcinoma cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925659/ https://www.ncbi.nlm.nih.gov/pubmed/24025359 http://dx.doi.org/10.4161/cbt.26110 |
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