Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer
AbstractCannabidiol, 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. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 359 KB)
Share & Cite This Article
Kim, J.L.; Kim, B.R.; Kim, D.Y.; Jeong, Y.A.; Jeong, S.; Na, Y.J.; Park, S.H.; Yun, H.K.; Jo, M.J.; Kim, B.G.; Kim, H.D.; Kim, D.H.; Oh, S.C.; Lee, S.I.; Lee, D.-H. Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer. Cancers 2019, 11, 642.
Kim JL, Kim BR, Kim DY, Jeong YA, Jeong S, Na YJ, Park SH, Yun HK, Jo MJ, Kim BG, Kim HD, Kim DH, Oh SC, Lee SI, Lee D-H. Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer. Cancers. 2019; 11(5):642.Chicago/Turabian Style
Kim, Jung L.; Kim, Bo R.; Kim, Dae Y.; Jeong, Yoon A.; Jeong, Soyeon; Na, Yoo J.; Park, Seong H.; Yun, Hye K.; Jo, Min J.; Kim, Bu G.; Kim, Han D.; Kim, Dae H.; Oh, Sang C.; Lee, Sun I.; Lee, Dae-Hee. 2019. "Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer." Cancers 11, no. 5: 642.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.