Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Apoptosis Regulatory Proteins
/ metabolism
Cannabidiol
/ pharmacology
Cell Line, Tumor
Colorectal Neoplasms
/ drug therapy
HCT116 Cells
Humans
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ drug effects
Apoptotic cell death
Bcl-2 protein family
Colon cancer
Marijuana extract
ROS
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
10 04 2019
10 04 2019
Historique:
received:
02
08
2018
revised:
21
12
2018
accepted:
11
01
2019
pubmed:
21
1
2019
medline:
18
12
2019
entrez:
21
1
2019
Statut:
ppublish
Résumé
Cannabidiol (CBD), one of the compounds present in the marijuana plant, has anti-tumor properties, but its mechanism is not well known. This study aimed to evaluate the apoptotic action of CBD in colorectal cancer (CRC) cells, and focused on its effects on the novel pro-apoptotic Noxa-reactive oxygen species (ROS) signaling pathway. CBD experiments were performed using the CRC cell lines HCT116 and DLD-1. CBD induced apoptosis by regulating many pro- and anti-apoptotic proteins, of which Noxa showed significantly higher expression. To understand the relationship between Noxa and CBD-induced apoptosis, Noxa levels were downregulated using siRNA, and the expression of apoptosis markers decreased. After ROS production was blocked, the level of Noxa also decreased, suggesting that ROS is involved in the regulation of Noxa, which along with ROS is a well-known pro-apoptotic signaling agents. As a result, CBD induced apoptosis in a Noxa-and-ROS-dependent manner. Taken together, the results obtained in this study re-demonstrated the effects of CBD treatment in vivo, thus confirming its role as a novel, reliable anticancer drug.
Identifiants
pubmed: 30660647
pii: S0304-3835(19)30023-0
doi: 10.1016/j.canlet.2019.01.011
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Apoptosis Regulatory Proteins
0
PMAIP1 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
Reactive Oxygen Species
0
Cannabidiol
19GBJ60SN5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12-23Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.