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Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety
Oxidative stress is known to play an important role in oral cancer development. In this study we aimed to examine whether a chemical activator of NRF2, sulforaphane (SFN), may have chemopreventive effects on oxidative stress-associated oral carcinogenesis. We first showed that Nrf2 activation and ox...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288201/ https://www.ncbi.nlm.nih.gov/pubmed/27447968 http://dx.doi.org/10.18632/oncotarget.10609 |
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author | Lan, Aixian Li, Wenjun Liu, Yao Xiong, Zhaohui Zhang, Xinyan Zhou, Shanshan Palko, Olesya Chen, Hao Kapita, Mayanga Prigge, Justin R. Schmidt, Edward E. Chen, Xin Sun, Zheng Chen, Xiaoxin Luke |
author_facet | Lan, Aixian Li, Wenjun Liu, Yao Xiong, Zhaohui Zhang, Xinyan Zhou, Shanshan Palko, Olesya Chen, Hao Kapita, Mayanga Prigge, Justin R. Schmidt, Edward E. Chen, Xin Sun, Zheng Chen, Xiaoxin Luke |
author_sort | Lan, Aixian |
collection | PubMed |
description | Oxidative stress is known to play an important role in oral cancer development. In this study we aimed to examine whether a chemical activator of NRF2, sulforaphane (SFN), may have chemopreventive effects on oxidative stress-associated oral carcinogenesis. We first showed that Nrf2 activation and oxidative damage were commonly seen in human samples of oral leukoplakia. With gene microarray and immunostaining, we found 4-nitroquinoline 1-oxide (4NQO) in drink activated the Nrf2 pathway and produced oxidative damage in mouse tongue. Meanwhile whole exome sequencing of mouse tongue identified mutations consistent with 4NQO's mutagenic profile. Using cultured human oral keratinocytes and 4NQO-treated mouse tongue, we found that SFN pre-treatment activated the NRF2 pathway and inhibited oxidative damage both in vitro and in vivo. On the contrary, a structural analogue of SFN without the isothiocyanate moiety did not have such effects. In a long-term chemoprevention study using wild-type and Nrf2(-/-) mice, we showed that topical application of SFN activated the NRF2 pathway, inhibited oxidative damage, and prevented 4NQO-induced oral carcinogenesis in an Nrf2-dependent manner. Our data clearly demonstrate that SFN has chemopreventive effects on oxidative stress-associated oral carcinogenesis, and such effects depend on Nrf2 and the isothiocyanate moiety. |
format | Online Article Text |
id | pubmed-5288201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52882012017-02-07 Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety Lan, Aixian Li, Wenjun Liu, Yao Xiong, Zhaohui Zhang, Xinyan Zhou, Shanshan Palko, Olesya Chen, Hao Kapita, Mayanga Prigge, Justin R. Schmidt, Edward E. Chen, Xin Sun, Zheng Chen, Xiaoxin Luke Oncotarget Research Paper Oxidative stress is known to play an important role in oral cancer development. In this study we aimed to examine whether a chemical activator of NRF2, sulforaphane (SFN), may have chemopreventive effects on oxidative stress-associated oral carcinogenesis. We first showed that Nrf2 activation and oxidative damage were commonly seen in human samples of oral leukoplakia. With gene microarray and immunostaining, we found 4-nitroquinoline 1-oxide (4NQO) in drink activated the Nrf2 pathway and produced oxidative damage in mouse tongue. Meanwhile whole exome sequencing of mouse tongue identified mutations consistent with 4NQO's mutagenic profile. Using cultured human oral keratinocytes and 4NQO-treated mouse tongue, we found that SFN pre-treatment activated the NRF2 pathway and inhibited oxidative damage both in vitro and in vivo. On the contrary, a structural analogue of SFN without the isothiocyanate moiety did not have such effects. In a long-term chemoprevention study using wild-type and Nrf2(-/-) mice, we showed that topical application of SFN activated the NRF2 pathway, inhibited oxidative damage, and prevented 4NQO-induced oral carcinogenesis in an Nrf2-dependent manner. Our data clearly demonstrate that SFN has chemopreventive effects on oxidative stress-associated oral carcinogenesis, and such effects depend on Nrf2 and the isothiocyanate moiety. Impact Journals LLC 2016-07-15 /pmc/articles/PMC5288201/ /pubmed/27447968 http://dx.doi.org/10.18632/oncotarget.10609 Text en Copyright: © 2016 Lan 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 Lan, Aixian Li, Wenjun Liu, Yao Xiong, Zhaohui Zhang, Xinyan Zhou, Shanshan Palko, Olesya Chen, Hao Kapita, Mayanga Prigge, Justin R. Schmidt, Edward E. Chen, Xin Sun, Zheng Chen, Xiaoxin Luke Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title | Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title_full | Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title_fullStr | Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title_full_unstemmed | Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title_short | Chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on NRF2 and the isothiocyanate moiety |
title_sort | chemoprevention of oxidative stress-associated oral carcinogenesis by sulforaphane depends on nrf2 and the isothiocyanate moiety |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288201/ https://www.ncbi.nlm.nih.gov/pubmed/27447968 http://dx.doi.org/10.18632/oncotarget.10609 |
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