Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer
Cannabidiol, a major non-psychotomimetic compound derived from <i>Cannabis sativa</i>, 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-rel...
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doaj-6316eca70e2d4f3aad635189644a0b922020-11-24T21:44:25ZengMDPI AGCancers2072-66942019-05-0111564210.3390/cancers11050642cancers11050642Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal CancerJung Lim Kim0Bo Ram Kim1Dae Yeong Kim2Yoon A. Jeong3Soyeon Jeong4Yoo Jin Na5Seong Hye Park6Hye Kyeong Yun7Min Jee Jo8Bu Gyeom Kim9Han Do Kim10Dae Hyun Kim11Sang Cheul Oh12Sun Il Lee13Dae-Hee Lee14Division of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, KoreaDivision of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaDivision of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaGraduate School of Medicine, Korea University College of Medicine, Seoul 02841, KoreaKaiyon Bio Tech Co., Ltd, 226 Gamasan-Ro, Guro-gu, Seoul 08308, KoreaKaiyon Bio Tech Co., Ltd, 226 Gamasan-Ro, Guro-gu, Seoul 08308, KoreaDivision of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, KoreaDepartment of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, KoreaDivision of Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University Guro Hospital, Seoul 08308, KoreaCannabidiol, a major non-psychotomimetic compound derived from <i>Cannabis sativa</i>, 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.https://www.mdpi.com/2072-6694/11/5/642cannabidiolTNF-related apoptosis-inducing liganddeath receptor 5endoplasmic reticulum stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jung Lim Kim Bo Ram Kim Dae Yeong Kim Yoon A. Jeong Soyeon Jeong Yoo Jin Na Seong Hye Park Hye Kyeong Yun Min Jee Jo Bu Gyeom Kim Han Do Kim Dae Hyun Kim Sang Cheul Oh Sun Il Lee Dae-Hee Lee |
spellingShingle |
Jung Lim Kim Bo Ram Kim Dae Yeong Kim Yoon A. Jeong Soyeon Jeong Yoo Jin Na Seong Hye Park Hye Kyeong Yun Min Jee Jo Bu Gyeom Kim Han Do Kim Dae Hyun Kim Sang Cheul Oh Sun Il Lee Dae-Hee Lee Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer Cancers cannabidiol TNF-related apoptosis-inducing ligand death receptor 5 endoplasmic reticulum stress |
author_facet |
Jung Lim Kim Bo Ram Kim Dae Yeong Kim Yoon A. Jeong Soyeon Jeong Yoo Jin Na Seong Hye Park Hye Kyeong Yun Min Jee Jo Bu Gyeom Kim Han Do Kim Dae Hyun Kim Sang Cheul Oh Sun Il Lee Dae-Hee Lee |
author_sort |
Jung Lim Kim |
title |
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
title_short |
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
title_full |
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
title_fullStr |
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
title_full_unstemmed |
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer |
title_sort |
cannabidiol enhances the therapeutic effects of trail by upregulating dr5 in colorectal cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-05-01 |
description |
Cannabidiol, a major non-psychotomimetic compound derived from <i>Cannabis sativa</i>, 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. |
topic |
cannabidiol TNF-related apoptosis-inducing ligand death receptor 5 endoplasmic reticulum stress |
url |
https://www.mdpi.com/2072-6694/11/5/642 |
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