Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
Identifieur interne : 000879 ( Main/Exploration ); précédent : 000878; suivant : 000880Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer
Auteurs : Soyeon Jeong [Corée du Sud] ; Dae Yeong Kim [Corée du Sud] ; Sang Hee Kang [Corée du Sud] ; Hye Kyeong Yun [Corée du Sud] ; Jung Lim Kim [Corée du Sud] ; Bo Ram Kim [Corée du Sud] ; Seong Hye Park [Corée du Sud] ; Yoo Jin Na [Corée du Sud] ; Min Jee Jo [Corée du Sud] ; Yoon A. Jeong [Corée du Sud] ; Bu Gyeom Kim [Corée du Sud] ; Dae-Hee Lee [Corée du Sud] ; Sang Cheul Oh [Corée du Sud]Source :
- Cancers [ 2072-6694 ] ; 2019.
Abstract
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.
Url:
DOI: 10.3390/cancers11070982
PubMed: 31337142
PubMed Central: 6678695
Affiliations:
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Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Dae Yeong" sort="Kim, Dae Yeong" uniqKey="Kim D" first="Dae Yeong" last="Kim">Dae Yeong Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kang, Sang Hee" sort="Kang, Sang Hee" uniqKey="Kang S" first="Sang Hee" last="Kang">Sang Hee Kang</name><affiliation wicri:level="1"><nlm:aff id="af3-cancers-11-00982">Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Yun, Hye Kyeong" sort="Yun, Hye Kyeong" uniqKey="Yun H" first="Hye Kyeong" last="Yun">Hye Kyeong Yun</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Jung Lim" sort="Kim, Jung Lim" uniqKey="Kim J" first="Jung Lim" last="Kim">Jung Lim Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-cancers-11-00982">Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Bo Ram" sort="Kim, Bo Ram" uniqKey="Kim B" first="Bo Ram" last="Kim">Bo Ram Kim</name><affiliation wicri:level="1"><nlm:aff id="af1-cancers-11-00982">Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Park, Seong Hye" sort="Park, Seong Hye" uniqKey="Park S" first="Seong Hye" last="Park">Seong Hye Park</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Na, Yoo Jin" sort="Na, Yoo Jin" uniqKey="Na Y" first="Yoo Jin" last="Na">Yoo Jin Na</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Jo, Min Jee" sort="Jo, Min Jee" uniqKey="Jo M" first="Min Jee" last="Jo">Min Jee Jo</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Jeong, Yoon A" sort="Jeong, Yoon A" uniqKey="Jeong Y" first="Yoon A." last="Jeong">Yoon A. Jeong</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Kim, Bu Gyeom" sort="Kim, Bu Gyeom" uniqKey="Kim B" first="Bu Gyeom" last="Kim">Bu Gyeom Kim</name><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Lee, Dae Hee" sort="Lee, Dae Hee" uniqKey="Lee D" first="Dae-Hee" last="Lee">Dae-Hee Lee</name><affiliation wicri:level="1"><nlm:aff id="af1-cancers-11-00982">Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Oh, Sang Cheul" sort="Oh, Sang Cheul" uniqKey="Oh S" first="Sang Cheul" last="Oh">Sang Cheul Oh</name><affiliation wicri:level="1"><nlm:aff id="af1-cancers-11-00982">Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-cancers-11-00982">Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></analytic><series><title level="j">Cancers</title><idno type="eISSN">2072-6694</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Siegel, R L" uniqKey="Siegel R">R.L. Siegel</name></author><author><name sortKey="Miller, K D" uniqKey="Miller K">K.D. Miller</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A. Jemal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bendell, J C" uniqKey="Bendell J">J.C. Bendell</name></author><author><name sortKey="Bekaii Saab, T S" uniqKey="Bekaii Saab T">T.S. Bekaii-Saab</name></author><author><name sortKey="Cohn, A L" uniqKey="Cohn A">A.L. Cohn</name></author><author><name sortKey="Hurwitz, H I" uniqKey="Hurwitz H">H.I. Hurwitz</name></author><author><name sortKey="Kozloff, M" uniqKey="Kozloff M">M. Kozloff</name></author><author><name sortKey="Tezcan, H" uniqKey="Tezcan H">H. Tezcan</name></author><author><name sortKey="Roach, N" uniqKey="Roach N">N. 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Yun</name></author><author><name sortKey="Jeong, Y A" uniqKey="Jeong Y">Y.A. Jeong</name></author><author><name sortKey="Jo, M J" uniqKey="Jo M">M.J. Jo</name></author><author><name sortKey="Kang, S H" uniqKey="Kang S">S.H. Kang</name></author><author><name sortKey="Kim, J L" uniqKey="Kim J">J.L. Kim</name></author><author><name sortKey="Kim, D Y" uniqKey="Kim D">D.Y. Kim</name></author><author><name sortKey="Park, S H" uniqKey="Park S">S.H. Park</name></author><author><name sortKey="Kim, B R" uniqKey="Kim B">B.R. Kim</name></author><author><name sortKey="Na, Y J" uniqKey="Na Y">Y.J. Na</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Jeong, Soyeon" sort="Jeong, Soyeon" uniqKey="Jeong S" first="Soyeon" last="Jeong">Soyeon Jeong</name></region><name sortKey="Jeong, Yoon A" sort="Jeong, Yoon A" uniqKey="Jeong Y" first="Yoon A." last="Jeong">Yoon A. Jeong</name><name sortKey="Jo, Min Jee" sort="Jo, Min Jee" uniqKey="Jo M" first="Min Jee" last="Jo">Min Jee Jo</name><name sortKey="Kang, Sang Hee" sort="Kang, Sang Hee" uniqKey="Kang S" first="Sang Hee" last="Kang">Sang Hee Kang</name><name sortKey="Kim, Bo Ram" sort="Kim, Bo Ram" uniqKey="Kim B" first="Bo Ram" last="Kim">Bo Ram Kim</name><name sortKey="Kim, Bu Gyeom" sort="Kim, Bu Gyeom" uniqKey="Kim B" first="Bu Gyeom" last="Kim">Bu Gyeom Kim</name><name sortKey="Kim, Dae Yeong" sort="Kim, Dae Yeong" uniqKey="Kim D" first="Dae Yeong" last="Kim">Dae Yeong Kim</name><name sortKey="Kim, Jung Lim" sort="Kim, Jung Lim" uniqKey="Kim J" first="Jung Lim" last="Kim">Jung Lim Kim</name><name sortKey="Lee, Dae Hee" sort="Lee, Dae Hee" uniqKey="Lee D" first="Dae-Hee" last="Lee">Dae-Hee Lee</name><name sortKey="Lee, Dae Hee" sort="Lee, Dae Hee" uniqKey="Lee D" first="Dae-Hee" last="Lee">Dae-Hee Lee</name><name sortKey="Na, Yoo Jin" sort="Na, Yoo Jin" uniqKey="Na Y" first="Yoo Jin" last="Na">Yoo Jin Na</name><name sortKey="Oh, Sang Cheul" sort="Oh, Sang Cheul" uniqKey="Oh S" first="Sang Cheul" last="Oh">Sang Cheul Oh</name><name sortKey="Oh, Sang Cheul" sort="Oh, Sang Cheul" uniqKey="Oh S" first="Sang Cheul" last="Oh">Sang Cheul Oh</name><name sortKey="Park, Seong Hye" sort="Park, Seong Hye" uniqKey="Park S" first="Seong Hye" last="Park">Seong Hye Park</name><name sortKey="Yun, Hye Kyeong" sort="Yun, Hye Kyeong" uniqKey="Yun H" first="Hye Kyeong" last="Yun">Hye Kyeong Yun</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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