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Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src
The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM(™) chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764254/ https://www.ncbi.nlm.nih.gov/pubmed/29324748 http://dx.doi.org/10.1371/journal.pone.0189524 |
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author | Shahzad, Mian M. K. Felder, Mildred Ludwig, Kai Van Galder, Hannah R. Anderson, Matthew L. Kim, Jong Cook, Mark E. Kapur, Arvinder K. Patankar, Manish S. |
author_facet | Shahzad, Mian M. K. Felder, Mildred Ludwig, Kai Van Galder, Hannah R. Anderson, Matthew L. Kim, Jong Cook, Mark E. Kapur, Arvinder K. Patankar, Manish S. |
author_sort | Shahzad, Mian M. K. |
collection | PubMed |
description | The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM(™) chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC(50), 7 μM) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3β and loss of β-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10,c12 CLA—mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr(416). Due to its ability to inhibit proliferation and migration, t10,c12 CLA should be considered for treatment of ovarian cancer. |
format | Online Article Text |
id | pubmed-5764254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57642542018-01-23 Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src Shahzad, Mian M. K. Felder, Mildred Ludwig, Kai Van Galder, Hannah R. Anderson, Matthew L. Kim, Jong Cook, Mark E. Kapur, Arvinder K. Patankar, Manish S. PLoS One Research Article The goal of this study was to investigate the anti-cancer effects of Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCM(™) chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the proliferation and migration and invasion of cancer cells. qPCR and Western Blotting were used to determine the expression of specific factors. RNA sequencing was conducted using the Illumina platform and apoptosis was measured using a flow cytometry assay. t10,c12 CLA (IC(50), 7 μM) inhibited proliferation of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the proliferation of these cells. Transcription of 165 genes was significantly repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal degradation of misfolded proteins, were downregulated upon treatment. While apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated cells was correlated with phosphorylation of GSK3β and loss of β-catenin. microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1 arrest by downregulating E2F1. miR215 upregulation was correlated with increased expression of p27/Kip-1. t10,c12 CLA—mediated inhibition of invasion and migration correlated with decreased expression of PTP1b and decreased Src activation by inhibiting phosphorylation at Tyr(416). Due to its ability to inhibit proliferation and migration, t10,c12 CLA should be considered for treatment of ovarian cancer. Public Library of Science 2018-01-11 /pmc/articles/PMC5764254/ /pubmed/29324748 http://dx.doi.org/10.1371/journal.pone.0189524 Text en © 2018 Shahzad 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 Shahzad, Mian M. K. Felder, Mildred Ludwig, Kai Van Galder, Hannah R. Anderson, Matthew L. Kim, Jong Cook, Mark E. Kapur, Arvinder K. Patankar, Manish S. Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title | Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title_full | Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title_fullStr | Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title_full_unstemmed | Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title_short | Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src |
title_sort | trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of ovarian cancer cells by inducing er stress, autophagy, and modulation of src |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764254/ https://www.ncbi.nlm.nih.gov/pubmed/29324748 http://dx.doi.org/10.1371/journal.pone.0189524 |
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