Next Article in Journal
Impact of Technique and Schedule of Reirradiation Plus Hyperthermia on Outcome after Surgery for Patients with Recurrent Breast Cancer
Next Article in Special Issue
Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer
Previous Article in Journal
Gold as a Possible Alternative to Platinum-Based Chemotherapy for Colon Cancer Treatment
Previous Article in Special Issue
Targeting ATG4 in Cancer Therapy
Open AccessArticle

Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells

Division of Oncology/Hematology, Department of Internal Medicine, Korea University Guro Hospital, 148, Gurodong-gil, Guro-gu, Seoul 08308, Korea
Graduate School of Medicine, College of Medicine, Korea University, Seoul 08308, Korea
Division of Oncology, Department of Internal Medicine, Kyung Hee University School of Medicine, 23 Kyung Hee dae-ro, Dong-dae-mun-gu, Seoul 02447, Korea
Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea
Kaiyon Bio Tech Co., Ltd, 226 Gamasan-Ro, Guro-gu, Seoul 08308, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(6), 781;
Received: 9 May 2019 / Revised: 3 June 2019 / Accepted: 4 June 2019 / Published: 5 June 2019
(This article belongs to the Special Issue The Role of Autophagy in Cancer Progression and Drug Resistance)
PDF [8249 KB, uploaded 21 June 2019]


Although oxaliplatin is an effective chemotherapeutic drug for colorectal cancer (CRC) treatment, patients often develop resistance to it. Therefore, a new strategy for CRC treatment is needed. The purpose of this study was to determine the effect of cannabidiol (CBD), one of the components of the cannabis plant, in overcoming oxaliplatin resistance in CRC cells. We established oxaliplatin-resistant cell lines, DLD-1 R and colo205 R, in CRC DLD-1 and colo205 cells. Autophagic cell death was induced when oxaliplatin-resistant cells were treated with both oxaliplatin and CBD. Additionally, phosphorylation of nitric oxide synthase 3 (NOS3) was increased in oxaliplatin-resistant cells compared to that in parent cells. Combined treatment with oxaliplatin and CBD reduced phospho-NOS3 levels and nitric oxide (NO) production and resulted in the production of reactive oxygen species (ROS) by reducing the levels of superoxide dismutase 2, an antioxidant present in the mitochondria, causing mitochondrial dysfunction. Taken together, these results suggest that elevated phosphorylation of NOS3 is essential for oxaliplatin resistance. The combination of oxaliplatin and CBD decreased NOS3 phosphorylation, which resulted in autophagy, by inducing the overproduction of ROS through mitochondrial dysfunction, thus overcoming oxaliplatin resistance. View Full-Text
Keywords: oxaliplatin resistance; colorectal cancer; CBD; NOS3; autophagy; mitochondrial dysfunction oxaliplatin resistance; colorectal cancer; CBD; NOS3; autophagy; mitochondrial dysfunction

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).

Share & Cite This Article

MDPI and ACS Style

Jeong, S.; Kim, B.G.; Kim, D.Y.; Kim, B.R.; Kim, J.L.; Park, S.H.; Na, Y.J.; Jo, M.J.; Yun, H.K.; Jeong, Y.A.; Kim, H.J.; Lee, S.I.; Kim, H.D.; Kim, D.H.; Oh, S.C.; Lee, D.-H. Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells. Cancers 2019, 11, 781.

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



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