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Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer

Oxaliplatin is an anticancer drug administered to colorectal cancer (CRC) patients in combination with 5-fluorouracil and antibodies (bevacizumab and cetuximab), thereby significantly improving the survival rate of CRC. However, due to various side effects associated with the above treatment strateg...

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Autores principales: Jeong, Soyeon, Kim, Dae Yeong, Kang, Sang Hee, Yun, Hye Kyeong, Kim, Jung Lim, Kim, Bo Ram, Park, Seong Hye, Na, Yoo Jin, Jo, Min Jee, Jeong, Yoon A., Kim, Bu Gyeom, Lee, Dae-Hee, Oh, Sang Cheul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678695/
https://www.ncbi.nlm.nih.gov/pubmed/31337142
http://dx.doi.org/10.3390/cancers11070982
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author Jeong, Soyeon
Kim, Dae Yeong
Kang, Sang Hee
Yun, Hye Kyeong
Kim, Jung Lim
Kim, Bo Ram
Park, Seong Hye
Na, Yoo Jin
Jo, Min Jee
Jeong, Yoon A.
Kim, Bu Gyeom
Lee, Dae-Hee
Oh, Sang Cheul
author_facet Jeong, Soyeon
Kim, Dae Yeong
Kang, Sang Hee
Yun, Hye Kyeong
Kim, Jung Lim
Kim, Bo Ram
Park, Seong Hye
Na, Yoo Jin
Jo, Min Jee
Jeong, Yoon A.
Kim, Bu Gyeom
Lee, Dae-Hee
Oh, Sang Cheul
author_sort Jeong, Soyeon
collection PubMed
description Oxaliplatin is an anticancer drug administered to colorectal cancer (CRC) patients in combination with 5-fluorouracil and antibodies (bevacizumab and cetuximab), thereby significantly improving the survival rate of CRC. However, due to various side effects associated with the above treatment strategy, the need for combinatorial therapeutic strategies has emerged. Based on the demand for new combinatorial therapies and the known antitumor effects of the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), we investigated the Oxaliplatin and DHA combination for its effect. Our results indicated that DHA further enhanced Oxaliplatin-induced cell viability and autophagic cell death, in vitro and in vivo. Oxaliplatin and DHA also increased the expression of Sestrin 2 (SESN2) and endoplasmic reticulum (ER) stress related C/EBP homologous protein (CHOP). Additionally, treatment with Oxaliplatin and DHA enhanced the binding of CHOP to the promotor region of SESN2, increasing SESN2 expression. These results suggested that DHA enhanced Oxaliplatin-induced reduction in cell viability and increase in autophagy via activating SESN2 and increasing ER stress. Thus, SESN2 may be an effective preclinical target for CRC treatment.
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spelling pubmed-66786952019-08-19 Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer Jeong, Soyeon Kim, Dae Yeong Kang, Sang Hee Yun, Hye Kyeong Kim, Jung Lim Kim, Bo Ram Park, Seong Hye Na, Yoo Jin Jo, Min Jee Jeong, Yoon A. Kim, Bu Gyeom Lee, Dae-Hee Oh, Sang Cheul Cancers (Basel) Article Oxaliplatin is an anticancer drug administered to colorectal cancer (CRC) patients in combination with 5-fluorouracil and antibodies (bevacizumab and cetuximab), thereby significantly improving the survival rate of CRC. However, due to various side effects associated with the above treatment strategy, the need for combinatorial therapeutic strategies has emerged. Based on the demand for new combinatorial therapies and the known antitumor effects of the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), we investigated the Oxaliplatin and DHA combination for its effect. Our results indicated that DHA further enhanced Oxaliplatin-induced cell viability and autophagic cell death, in vitro and in vivo. Oxaliplatin and DHA also increased the expression of Sestrin 2 (SESN2) and endoplasmic reticulum (ER) stress related C/EBP homologous protein (CHOP). Additionally, treatment with Oxaliplatin and DHA enhanced the binding of CHOP to the promotor region of SESN2, increasing SESN2 expression. These results suggested that DHA enhanced Oxaliplatin-induced reduction in cell viability and increase in autophagy via activating SESN2 and increasing ER stress. Thus, SESN2 may be an effective preclinical target for CRC treatment. MDPI 2019-07-14 /pmc/articles/PMC6678695/ /pubmed/31337142 http://dx.doi.org/10.3390/cancers11070982 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeong, Soyeon
Kim, Dae Yeong
Kang, Sang Hee
Yun, Hye Kyeong
Kim, Jung Lim
Kim, Bo Ram
Park, Seong Hye
Na, Yoo Jin
Jo, Min Jee
Jeong, Yoon A.
Kim, Bu Gyeom
Lee, Dae-Hee
Oh, Sang Cheul
Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title_full Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title_fullStr Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title_full_unstemmed Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title_short Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
title_sort docosahexaenoic acid enhances oxaliplatin-induced autophagic cell death via the er stress/sesn2 pathway in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678695/
https://www.ncbi.nlm.nih.gov/pubmed/31337142
http://dx.doi.org/10.3390/cancers11070982
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