Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

Abstract Transcription factor AP-1 plays a central role in HPV-mediated cervical carcinogenesis. AP-1 has also been implicated in chemo-radio-resistance but the mechanism(s) remained unexplored. In the present study, cervical cancer stem-like cells (CaCxSLCs) isolated and enriched from cervical canc...

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Autores principales:	Abhishek Tyagi, Kanchan Vishnoi, Harsimrut Kaur, Yogesh Srivastava, Bal Gangadhar Roy, Bhudev C. Das, Alok C. Bharti
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fbfd8f53e8eb4548be01f4d41a4ab6be
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spelling	oai:doaj.org-article:fbfd8f53e8eb4548be01f4d41a4ab6be2021-12-02T11:40:52ZCervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity10.1038/s41598-017-05162-x2045-2322https://doaj.org/article/fbfd8f53e8eb4548be01f4d41a4ab6be2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05162-xhttps://doaj.org/toc/2045-2322Abstract Transcription factor AP-1 plays a central role in HPV-mediated cervical carcinogenesis. AP-1 has also been implicated in chemo-radio-resistance but the mechanism(s) remained unexplored. In the present study, cervical cancer stem-like cells (CaCxSLCs) isolated and enriched from cervical cancer cell lines SiHa and C33a demonstrated an elevated AP-1 DNA-binding activity in comparison to non-stem cervical cancer cells. Upon UV-irradiation, CaCxSLCs showed a UV exposure duration-dependent higher proliferation and highly increased AP-1 activity whereas it was completely abolished in non-stem cancer cells. CaCxSLCs also showed differential overexpression of c-Fos and c-Jun at transcript as well as in protein level. The loss of AP-1 activity and expression was accompanied by decrease in cell viability and proliferation in UV-irradiated non-stem cancer cells. Interestingly, CaCxSLCs treated with curcumin prior to UV-irradiation abolished AP-1 activity and a concomitant reduction in SP cells leading to abrogation of sphere forming ability, loss of proliferation, induction of apoptosis and the cells were poorly tumorigenic. The curcumin pre-treatment abolished the expression of c-Fos and c-Jun but upregulated Fra-1 expression in UV-irradiated CaCxSLCs. Thus, the study suggests a critical role of AP-1 protein in the manifestation of radioresistance but targeting with curcumin helps in radiosensitizing CaCxSLCs through upregulation of Fra-1.Abhishek TyagiKanchan VishnoiHarsimrut KaurYogesh SrivastavaBal Gangadhar RoyBhudev C. DasAlok C. BhartiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abhishek Tyagi Kanchan Vishnoi Harsimrut Kaur Yogesh Srivastava Bal Gangadhar Roy Bhudev C. Das Alok C. Bharti Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
description	Abstract Transcription factor AP-1 plays a central role in HPV-mediated cervical carcinogenesis. AP-1 has also been implicated in chemo-radio-resistance but the mechanism(s) remained unexplored. In the present study, cervical cancer stem-like cells (CaCxSLCs) isolated and enriched from cervical cancer cell lines SiHa and C33a demonstrated an elevated AP-1 DNA-binding activity in comparison to non-stem cervical cancer cells. Upon UV-irradiation, CaCxSLCs showed a UV exposure duration-dependent higher proliferation and highly increased AP-1 activity whereas it was completely abolished in non-stem cancer cells. CaCxSLCs also showed differential overexpression of c-Fos and c-Jun at transcript as well as in protein level. The loss of AP-1 activity and expression was accompanied by decrease in cell viability and proliferation in UV-irradiated non-stem cancer cells. Interestingly, CaCxSLCs treated with curcumin prior to UV-irradiation abolished AP-1 activity and a concomitant reduction in SP cells leading to abrogation of sphere forming ability, loss of proliferation, induction of apoptosis and the cells were poorly tumorigenic. The curcumin pre-treatment abolished the expression of c-Fos and c-Jun but upregulated Fra-1 expression in UV-irradiated CaCxSLCs. Thus, the study suggests a critical role of AP-1 protein in the manifestation of radioresistance but targeting with curcumin helps in radiosensitizing CaCxSLCs through upregulation of Fra-1.
format	article
author	Abhishek Tyagi Kanchan Vishnoi Harsimrut Kaur Yogesh Srivastava Bal Gangadhar Roy Bhudev C. Das Alok C. Bharti
author_facet	Abhishek Tyagi Kanchan Vishnoi Harsimrut Kaur Yogesh Srivastava Bal Gangadhar Roy Bhudev C. Das Alok C. Bharti
author_sort	Abhishek Tyagi
title	Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
title_short	Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
title_full	Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
title_fullStr	Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
title_full_unstemmed	Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity
title_sort	cervical cancer stem cells manifest radioresistance: association with upregulated ap-1 activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fbfd8f53e8eb4548be01f4d41a4ab6be
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Cervical cancer stem cells manifest radioresistance: Association with upregulated AP-1 activity

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