Next Article in Journal
Uncovering Potential Therapeutic Targets in Colorectal Cancer by Deciphering Mutational Status and Expression of Druggable Oncogenes
Previous Article in Journal
Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review
Article Menu

Export Article

Open AccessArticle

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

1
Department of Oncology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea
2
Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea
3
Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(7), 982; https://doi.org/10.3390/cancers11070982
Received: 7 May 2019 / Revised: 6 July 2019 / Accepted: 8 July 2019 / Published: 14 July 2019
(This article belongs to the Special Issue Cell Death in Cancer)
  |  
PDF [2428 KB, uploaded 14 July 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. View Full-Text
Keywords: Oxaliplatin; docosahexaenoic acid; Sestrin 2; autophagic cell death; colon cancer Oxaliplatin; docosahexaenoic acid; Sestrin 2; autophagic cell death; colon cancer
Figures

Graphical abstract

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 (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Jeong, S.; Kim, D.Y.; Kang, S.H.; Yun, H.K.; Kim, J.L.; Kim, B.R.; Park, S.H.; Na, Y.J.; Jo, M.J.; Jeong, Y.A.; Kim, B.G.; Lee, D.-H.; Oh, S.C. Docosahexaenoic Acid Enhances Oxaliplatin-Induced Autophagic Cell Death via the ER Stress/Sesn2 Pathway in Colorectal Cancer. Cancers 2019, 11, 982.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top