Docosahexaenoic acid enhances oxaliplatin-induced autophagic cell death via the ER stress/sesn2 pathway in colorectal cancer

Soyeon Jeong, Dae Yeong Kim, Sang Hee Kang, Hye Kyeong Yun, Jung Lim Kim, Bo Ram Kim, Seong Hye Park, Yoo Jin Na, Min Jee Jo, Yoon A. Jeong, Bu Gyeom Kim, Dae Hee Lee, Sang Cheul Oh

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Article number982
JournalCancers
Volume11
Issue number7
DOIs
Publication statusPublished - 2019 Jul

Keywords

  • Autophagic cell death
  • Colon cancer
  • Docosahexaenoic acid
  • Oxaliplatin
  • Sestrin 2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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