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Cancers (Basel). 2019 May 9;11(5). pii: E642. doi: 10.3390/cancers11050642.

Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer.

Author information

1
Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. clickkjl@naver.com.
2
Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. ilovewish777@naver.com.
3
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. derrickdyblue22@gmail.com.
4
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. leomi2614@naver.com.
5
Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. limlab7@gmail.com.
6
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. wing1278@naver.com.
7
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. psh3938@hanmail.net.
8
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. katecoco@hanmail.net.
9
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. minjeeyoyo@nate.com.
10
Graduate School of Medicine, Korea University College of Medicine, Seoul 02841, Korea. qnrua10047@naver.com.
11
Kaiyon Bio Tech Co., Ltd, 226 Gamasan-Ro, Guro-gu, Seoul 08308, Korea. howard@kaiyonbiotech.com.
12
Kaiyon Bio Tech Co., Ltd, 226 Gamasan-Ro, Guro-gu, Seoul 08308, Korea. dkim238@kaiyonbiotech.com.
13
Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. sachoh@korea.ac.kr.
14
Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Korea. jirisan@gmail.com.
15
Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, Korea. neogene@korea.ac.kr.

Abstract

Cannabidiol, a major non-psychotomimetic compound derived from Cannabis sativa, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.

KEYWORDS:

TNF-related apoptosis-inducing ligand; cannabidiol; death receptor 5; endoplasmic reticulum stress

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