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- Title
Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer.
- Authors
Kim, Jung Lim; Kim, Bo Ram; Kim, Dae Yeong; Jeong, Yoon A.; Jeong, Soyeon; Na, Yoo Jin; Park, Seong Hye; Yun, Hye Kyeong; Jo, Min Jee; Kim, Bu Gyeom; Kim, Han Do; Kim, Dae Hyun; Oh, Sang Cheul; Lee, Sun Il; Lee, Dae-Hee
- 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.
- Subjects
CANNABIS (Genus); CARRIER proteins; CELL lines; CELL physiology; CELL receptors; COLON tumors; DRUG synergism; GENE expression; MOLECULAR structure; PHOSPHORYLATION; PROTEIN kinases; RECTUM tumors; XENOGRAFTS; IN vitro studies
- Publication
Cancers, 2019, Vol 11, Issue 5, p642
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11050642