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CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells
We report anticarcinogenic effects of suicide gene therapy that relies on the use of resveratrol-responsive CArG elements from the Egr-1 promoter to induce GADD45α. In A549 lung cancer cells, endogenous GADD45α was not induced upon resveratrol treatment. Therefore, induction of exogenous GADD45α res...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482243/ https://www.ncbi.nlm.nih.gov/pubmed/26124921 |
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author | Shi, Qiwen Geldenhuys, Werner Sutariya, Vijaykumar Bishayee, Anupam Patel, Isha Bhatia, Deepak |
author_facet | Shi, Qiwen Geldenhuys, Werner Sutariya, Vijaykumar Bishayee, Anupam Patel, Isha Bhatia, Deepak |
author_sort | Shi, Qiwen |
collection | PubMed |
description | We report anticarcinogenic effects of suicide gene therapy that relies on the use of resveratrol-responsive CArG elements from the Egr-1 promoter to induce GADD45α. In A549 lung cancer cells, endogenous GADD45α was not induced upon resveratrol treatment. Therefore, induction of exogenous GADD45α resulted in growth inhibition. Resveratrol transiently induced Egr-1 through ERK/JNK-ElK-1. Hence, we cloned natural or synthetic Egr-1 promoter upstream of GADD45α cDNA to create a suicide gene therapy vector. Since natural promoter may have antagonized effects, we tested synthetic promoter that contains either five, six or nine repeats of CArG elements essential in the Egr-1 promoter to drive the expression of GADD45α upon resveratrol treatment. Further analysis confirmed that both synthetic promoter and natural Egr-1 promoter were able to “turn on” the expression of GADD45α when combined with resveratrol, and subsequently led to suppression of cell proliferation and apoptosis. |
format | Online Article Text |
id | pubmed-4482243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44822432015-06-29 CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells Shi, Qiwen Geldenhuys, Werner Sutariya, Vijaykumar Bishayee, Anupam Patel, Isha Bhatia, Deepak Genes Cancer Research Paper We report anticarcinogenic effects of suicide gene therapy that relies on the use of resveratrol-responsive CArG elements from the Egr-1 promoter to induce GADD45α. In A549 lung cancer cells, endogenous GADD45α was not induced upon resveratrol treatment. Therefore, induction of exogenous GADD45α resulted in growth inhibition. Resveratrol transiently induced Egr-1 through ERK/JNK-ElK-1. Hence, we cloned natural or synthetic Egr-1 promoter upstream of GADD45α cDNA to create a suicide gene therapy vector. Since natural promoter may have antagonized effects, we tested synthetic promoter that contains either five, six or nine repeats of CArG elements essential in the Egr-1 promoter to drive the expression of GADD45α upon resveratrol treatment. Further analysis confirmed that both synthetic promoter and natural Egr-1 promoter were able to “turn on” the expression of GADD45α when combined with resveratrol, and subsequently led to suppression of cell proliferation and apoptosis. Impact Journals LLC 2015-05 /pmc/articles/PMC4482243/ /pubmed/26124921 Text en Copyright: © 2015 Shi et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Shi, Qiwen Geldenhuys, Werner Sutariya, Vijaykumar Bishayee, Anupam Patel, Isha Bhatia, Deepak CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title | CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title_full | CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title_fullStr | CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title_full_unstemmed | CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title_short | CArG-driven GADD45α activated by resveratrol inhibits lung cancer cells |
title_sort | carg-driven gadd45α activated by resveratrol inhibits lung cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482243/ https://www.ncbi.nlm.nih.gov/pubmed/26124921 |
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