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The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53

Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA incre...

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Autores principales: Shin, Soyeon, Jing, Kaipeng, Jeong, Soyeon, Kim, Nayeong, Song, Kyoung-Sub, Heo, Jun-Young, Park, Ji-Hoon, Seo, Kang-Sik, Han, Jeongsu, Park, Jong-Il, Kweon, Gi-Ryang, Park, Seung-Kiel, Wu, Tong, Hwang, Byung-Doo, Lim, Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691929/
https://www.ncbi.nlm.nih.gov/pubmed/23841076
http://dx.doi.org/10.1155/2013/568671
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author Shin, Soyeon
Jing, Kaipeng
Jeong, Soyeon
Kim, Nayeong
Song, Kyoung-Sub
Heo, Jun-Young
Park, Ji-Hoon
Seo, Kang-Sik
Han, Jeongsu
Park, Jong-Il
Kweon, Gi-Ryang
Park, Seung-Kiel
Wu, Tong
Hwang, Byung-Doo
Lim, Kyu
author_facet Shin, Soyeon
Jing, Kaipeng
Jeong, Soyeon
Kim, Nayeong
Song, Kyoung-Sub
Heo, Jun-Young
Park, Ji-Hoon
Seo, Kang-Sik
Han, Jeongsu
Park, Jong-Il
Kweon, Gi-Ryang
Park, Seung-Kiel
Wu, Tong
Hwang, Byung-Doo
Lim, Kyu
author_sort Shin, Soyeon
collection PubMed
description Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA.
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spelling pubmed-36919292013-07-09 The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53 Shin, Soyeon Jing, Kaipeng Jeong, Soyeon Kim, Nayeong Song, Kyoung-Sub Heo, Jun-Young Park, Ji-Hoon Seo, Kang-Sik Han, Jeongsu Park, Jong-Il Kweon, Gi-Ryang Park, Seung-Kiel Wu, Tong Hwang, Byung-Doo Lim, Kyu Biomed Res Int Research Article Docosahexaenoic acid (DHA) induces autophagy-associated apoptotic cell death in wild-type p53 cancer cells via regulation of p53. The present study investigated the effects of DHA on PC3 and DU145 prostate cancer cell lines harboring mutant p53. Results show that, in addition to apoptosis, DHA increased the expression levels of lipidated form LC3B and potently stimulated the autophagic flux, suggesting that DHA induces both autophagy and apoptosis in cancer cells expressing mutant p53. DHA led to the generation of mitochondrial reactive oxygen species (ROS), as shown by the mitochondrial ROS-specific probe mitoSOX. Similarly, pretreatment with the antioxidant N-acetyl-cysteine (NAC) markedly inhibited both the autophagy and the apoptosis triggered by DHA, indicating that mitochondrial ROS mediate the cytotoxicity of DHA in mutant p53 cells. Further, DHA reduced the levels of phospho-Akt and phospho-mTOR in a concentration-dependent manner, while NAC almost completely blocked that effect. Collectively, these findings present a novel mechanism of ROS-regulated apoptosis and autophagy that involves Akt-mTOR signaling in prostate cancer cells with mutant p53 exposed to DHA. Hindawi Publishing Corporation 2013 2013-06-10 /pmc/articles/PMC3691929/ /pubmed/23841076 http://dx.doi.org/10.1155/2013/568671 Text en Copyright © 2013 Soyeon Shin et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Shin, Soyeon
Jing, Kaipeng
Jeong, Soyeon
Kim, Nayeong
Song, Kyoung-Sub
Heo, Jun-Young
Park, Ji-Hoon
Seo, Kang-Sik
Han, Jeongsu
Park, Jong-Il
Kweon, Gi-Ryang
Park, Seung-Kiel
Wu, Tong
Hwang, Byung-Doo
Lim, Kyu
The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title_full The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title_fullStr The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title_full_unstemmed The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title_short The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53
title_sort omega-3 polyunsaturated fatty acid dha induces simultaneous apoptosis and autophagy via mitochondrial ros-mediated akt-mtor signaling in prostate cancer cells expressing mutant p53
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691929/
https://www.ncbi.nlm.nih.gov/pubmed/23841076
http://dx.doi.org/10.1155/2013/568671
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