Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782504286747361280
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
work_keys_str_mv AT lanaixian chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT liwenjun chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT liuyao chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT xiongzhaohui chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT zhangxinyan chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT zhoushanshan chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT palkoolesya chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT chenhao chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT kapitamayanga chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT priggejustinr chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT schmidtedwarde chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT chenxin chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT sunzheng chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety
AT chenxiaoxinluke chemopreventionofoxidativestressassociatedoralcarcinogenesisbysulforaphanedependsonnrf2andtheisothiocyanatemoiety