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Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction

Biliary reflux has been considered a potential risk factor in upper aerodigestive tract malignancies. It is not yet clearly known how pH affects the bile‐induced activation of NF‐κB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applic...

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Autores principales: Doukas, Sotirios G., Cardoso, Bruno, Tower, Jacob I., Vageli, Dimitra P., Sasaki, Clarence T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675744/
https://www.ncbi.nlm.nih.gov/pubmed/31173474
http://dx.doi.org/10.1002/cam4.2194
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author Doukas, Sotirios G.
Cardoso, Bruno
Tower, Jacob I.
Vageli, Dimitra P.
Sasaki, Clarence T.
author_facet Doukas, Sotirios G.
Cardoso, Bruno
Tower, Jacob I.
Vageli, Dimitra P.
Sasaki, Clarence T.
author_sort Doukas, Sotirios G.
collection PubMed
description Biliary reflux has been considered a potential risk factor in upper aerodigestive tract malignancies. It is not yet clearly known how pH affects the bile‐induced activation of NF‐κB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applications of conjugated primary bile acids with unconjugated secondary bile acid, deoxycholic acid (DCA), on human hypopharyngeal primary cells reveal that strongly acidic pH (4.0) optimally enhances the tumorigenic effect of bile, by inducing activation of NF‐κB, STAT3 nuclear translocation, bcl‐2 overexpression and significant overexpression of the oncogenic mRNA phenotype, compared to weakly acidic pH (5.5) or neutral pH (7.0). As the pH becomes less acidic the partially activated primary bile acids and activated DCA begin to exert their influence; however, with significantly less intensity compared to bile acids at strongly acidic pH. Our findings suggest that biliary tumorigenic effect is strongly pH dependent. Controlling pH during reflux events may be therapeutically effective in reducing the potential risk of bile‐induced hypopharyngeal cancer.
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spelling pubmed-66757442019-08-06 Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction Doukas, Sotirios G. Cardoso, Bruno Tower, Jacob I. Vageli, Dimitra P. Sasaki, Clarence T. Cancer Med Cancer Biology Biliary reflux has been considered a potential risk factor in upper aerodigestive tract malignancies. It is not yet clearly known how pH affects the bile‐induced activation of NF‐κB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applications of conjugated primary bile acids with unconjugated secondary bile acid, deoxycholic acid (DCA), on human hypopharyngeal primary cells reveal that strongly acidic pH (4.0) optimally enhances the tumorigenic effect of bile, by inducing activation of NF‐κB, STAT3 nuclear translocation, bcl‐2 overexpression and significant overexpression of the oncogenic mRNA phenotype, compared to weakly acidic pH (5.5) or neutral pH (7.0). As the pH becomes less acidic the partially activated primary bile acids and activated DCA begin to exert their influence; however, with significantly less intensity compared to bile acids at strongly acidic pH. Our findings suggest that biliary tumorigenic effect is strongly pH dependent. Controlling pH during reflux events may be therapeutically effective in reducing the potential risk of bile‐induced hypopharyngeal cancer. John Wiley and Sons Inc. 2019-06-07 /pmc/articles/PMC6675744/ /pubmed/31173474 http://dx.doi.org/10.1002/cam4.2194 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Doukas, Sotirios G.
Cardoso, Bruno
Tower, Jacob I.
Vageli, Dimitra P.
Sasaki, Clarence T.
Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title_full Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title_fullStr Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title_full_unstemmed Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title_short Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction
title_sort biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by ph reduction
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675744/
https://www.ncbi.nlm.nih.gov/pubmed/31173474
http://dx.doi.org/10.1002/cam4.2194
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