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Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer

Homeostasis in eukaryotic tissues is tightly regulated by an intricate balance of the prosurvival and antisurvival signals. The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10), a dual-specificity phosphatase, plays a functional role in cell cycle arrest and apoptosis....

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Autores principales: Kansal, Shevali, Bhatnagar, Archana, Agnihotri, Navneet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885588/
https://www.ncbi.nlm.nih.gov/pubmed/24416253
http://dx.doi.org/10.1371/journal.pone.0084627
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author Kansal, Shevali
Bhatnagar, Archana
Agnihotri, Navneet
author_facet Kansal, Shevali
Bhatnagar, Archana
Agnihotri, Navneet
author_sort Kansal, Shevali
collection PubMed
description Homeostasis in eukaryotic tissues is tightly regulated by an intricate balance of the prosurvival and antisurvival signals. The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10), a dual-specificity phosphatase, plays a functional role in cell cycle arrest and apoptosis. NF-κB and its downstream regulators (such as VEGF) play a central role in prevention of apoptosis, promotion of inflammation and tumor growth. Therefore, we thought to estimate the expression of PTEN, Poly-ADP-ribose polymerase (PARP), NF-κBp50, NF-κBp65 and VEGF to evaluate the effect of supplementation of fish oil on apoptotic and inflammatory signaling in colon carcinoma. Male wistar rats in Group I received purified diet while Group II and III received modified diet supplemented with FO∶CO(1∶1)&FO∶CO(2.5∶1) respectively. These were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and that sacrificed after 16 weeks constituted post-initiation phase. We have analysed expression of PTEN, NF-κBp50, NF-κBp65 by flowcytometer and nuclear localization of NF-κB by immunofluorescence. PARP and VEGF were assessed by immunohistochemistry. In the initiation phase, animals receiving DMH have shown increased % of apoptotic cells, PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF however in post-initiation phase no significant alteration in apoptosis with decreased PTEN and increased PARP, NF-κBp50, NF-κBp65 and VEGF were observed as compared to control animals. On treatment with both ratios of fish oil in both the phases, augmentation in % of apoptotic cells, decreased PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF were documented with respect to DMH treated animals with effect being more exerted with higher ration in post-initiation phase. Hence, fish oil activates apoptosis, diminishes DNA damage and inhibits inflammatory signalling in a dose and time dependent manner so as to inhibit progression of colon cancer.
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spelling pubmed-38855882014-01-10 Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer Kansal, Shevali Bhatnagar, Archana Agnihotri, Navneet PLoS One Research Article Homeostasis in eukaryotic tissues is tightly regulated by an intricate balance of the prosurvival and antisurvival signals. The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10), a dual-specificity phosphatase, plays a functional role in cell cycle arrest and apoptosis. NF-κB and its downstream regulators (such as VEGF) play a central role in prevention of apoptosis, promotion of inflammation and tumor growth. Therefore, we thought to estimate the expression of PTEN, Poly-ADP-ribose polymerase (PARP), NF-κBp50, NF-κBp65 and VEGF to evaluate the effect of supplementation of fish oil on apoptotic and inflammatory signaling in colon carcinoma. Male wistar rats in Group I received purified diet while Group II and III received modified diet supplemented with FO∶CO(1∶1)&FO∶CO(2.5∶1) respectively. These were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and that sacrificed after 16 weeks constituted post-initiation phase. We have analysed expression of PTEN, NF-κBp50, NF-κBp65 by flowcytometer and nuclear localization of NF-κB by immunofluorescence. PARP and VEGF were assessed by immunohistochemistry. In the initiation phase, animals receiving DMH have shown increased % of apoptotic cells, PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF however in post-initiation phase no significant alteration in apoptosis with decreased PTEN and increased PARP, NF-κBp50, NF-κBp65 and VEGF were observed as compared to control animals. On treatment with both ratios of fish oil in both the phases, augmentation in % of apoptotic cells, decreased PTEN, PARP, NF-κBp50, NF-κBp65 and VEGF were documented with respect to DMH treated animals with effect being more exerted with higher ration in post-initiation phase. Hence, fish oil activates apoptosis, diminishes DNA damage and inhibits inflammatory signalling in a dose and time dependent manner so as to inhibit progression of colon cancer. Public Library of Science 2014-01-08 /pmc/articles/PMC3885588/ /pubmed/24416253 http://dx.doi.org/10.1371/journal.pone.0084627 Text en © 2014 Kansal 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kansal, Shevali
Bhatnagar, Archana
Agnihotri, Navneet
Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title_full Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title_fullStr Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title_full_unstemmed Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title_short Fish Oil Suppresses Cell Growth and Metastatic Potential by Regulating PTEN and NF-κB Signaling in Colorectal Cancer
title_sort fish oil suppresses cell growth and metastatic potential by regulating pten and nf-κb signaling in colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885588/
https://www.ncbi.nlm.nih.gov/pubmed/24416253
http://dx.doi.org/10.1371/journal.pone.0084627
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