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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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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. |
format | Online Article Text |
id | pubmed-3691929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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