Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number642
JournalCancers
Volume11
Issue number5
DOIs
Publication statusPublished - 2019 May 1

Fingerprint

Cannabidiol
TNF-Related Apoptosis-Inducing Ligand
Therapeutic Uses
Colorectal Neoplasms
Transcription Factor CHOP
Cannabis
Heat-Shock Proteins
Protein C
Heterografts
Neurodegenerative Diseases
Protein Kinases
Neoplasms
Chronic Disease
RNA
Apoptosis

Keywords

  • Cannabidiol
  • Death receptor 5
  • Endoplasmic reticulum stress
  • TNF-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kim, J. L., Kim, B. R., Kim, D. Y., Jeong, Y. A., Jeong, S., Na, Y. J., ... Lee, D. H. (2019). Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. Cancers, 11(5), [642]. https://doi.org/10.3390/cancers11050642

Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. / 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.

In: Cancers, Vol. 11, No. 5, 642, 01.05.2019.

Research output: Contribution to journalArticle

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, DH 2019, 'Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer', Cancers, vol. 11, no. 5, 642. https://doi.org/10.3390/cancers11050642
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. / Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer. In: Cancers. 2019 ; Vol. 11, No. 5.
@article{c6838e9717c14db7bc729c3cefbb0210,
title = "Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer",
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 = "Cannabidiol, Death receptor 5, Endoplasmic reticulum stress, TNF-related apoptosis-inducing ligand",
author = "Kim, {Jung Lim} and Kim, {Bo Ram} and Kim, {Dae Yeong} and Jeong, {Yoon A.} and Soyeon Jeong and Na, {Yoo Jin} and Park, {Seong Hye} and Yun, {Hye Kyeong} and Jo, {Min Jee} and Kim, {Bu Gyeom} and Kim, {Han Do} and Kim, {Dae Hyun} and Oh, {Sang Cheul} and Lee, {Sun Il} and Lee, {Dae Hee}",
year = "2019",
month = "5",
day = "1",
doi = "10.3390/cancers11050642",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "5",

}

TY - JOUR

T1 - Cannabidiol enhances the therapeutic effects of TRAIL by upregulating DR5 in colorectal cancer

AU - Kim, Jung Lim

AU - Kim, Bo Ram

AU - Kim, Dae Yeong

AU - Jeong, Yoon A.

AU - Jeong, Soyeon

AU - Na, Yoo Jin

AU - Park, Seong Hye

AU - Yun, Hye Kyeong

AU - Jo, Min Jee

AU - Kim, Bu Gyeom

AU - Kim, Han Do

AU - Kim, Dae Hyun

AU - Oh, Sang Cheul

AU - Lee, Sun Il

AU - Lee, Dae Hee

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Cannabidiol

KW - Death receptor 5

KW - Endoplasmic reticulum stress

KW - TNF-related apoptosis-inducing ligand

UR - http://www.scopus.com/inward/record.url?scp=85067038004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067038004&partnerID=8YFLogxK

U2 - 10.3390/cancers11050642

DO - 10.3390/cancers11050642

M3 - Article

AN - SCOPUS:85067038004

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 5

M1 - 642

ER -