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Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach

BACKGROUND: Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. MATERIALS & METHODS: In the current study, the chemotherapeutic activity of doxycycline...

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Autores principales: Nanda, Neha, Dhawan, Devinder K., Bhatia, Alka, Mahmood, Akhtar, Mahmood, Safrun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801417/
https://www.ncbi.nlm.nih.gov/pubmed/26998758
http://dx.doi.org/10.1371/journal.pone.0151539
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author Nanda, Neha
Dhawan, Devinder K.
Bhatia, Alka
Mahmood, Akhtar
Mahmood, Safrun
author_facet Nanda, Neha
Dhawan, Devinder K.
Bhatia, Alka
Mahmood, Akhtar
Mahmood, Safrun
author_sort Nanda, Neha
collection PubMed
description BACKGROUND: Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. MATERIALS & METHODS: In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. RESULTS: Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. CONCLUSION: These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.
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spelling pubmed-48014172016-03-23 Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach Nanda, Neha Dhawan, Devinder K. Bhatia, Alka Mahmood, Akhtar Mahmood, Safrun PLoS One Research Article BACKGROUND: Doxycycline (DOX) exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer. MATERIALS & METHODS: In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH) as well as study the effect of DOX-alone on a separate group of rats. RESULTS: Doxycycline administration in DMH-treated rats (DMH-DOX) unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers. CONCLUSION: These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects. Public Library of Science 2016-03-21 /pmc/articles/PMC4801417/ /pubmed/26998758 http://dx.doi.org/10.1371/journal.pone.0151539 Text en © 2016 Nanda et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nanda, Neha
Dhawan, Devinder K.
Bhatia, Alka
Mahmood, Akhtar
Mahmood, Safrun
Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title_full Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title_fullStr Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title_full_unstemmed Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title_short Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach
title_sort doxycycline promotes carcinogenesis & metastasis via chronic inflammatory pathway: an in vivo approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801417/
https://www.ncbi.nlm.nih.gov/pubmed/26998758
http://dx.doi.org/10.1371/journal.pone.0151539
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