Cannabidiol-induced apoptosis is mediated by activation of Noxa in human colorectal cancer cells

• Published in: Cancer letters Vol. 447; pp. 12 - 23
• Main Authors: Jeong, Soyeon, Yun, Hye Kyeong, Jeong, Yoon A, Jo, Min Jee, Kang, Sang Hee, Kim, Jung Lim, Kim, Dae Yeong, Park, Seong Hye, Kim, Bo Ram, Na, Yoo Jin, Lee, Sun Il, Kim, Han Do, Kim, Dae Hyun, Oh, Sang Cheul, Lee, Dae-Hee
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 10-04-2019; Elsevier Limited
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Apoptotic cell death; Bcl-2 protein family; Binding sites; Cancer therapies; Cannabidiol - pharmacology; Cannabinoids; Cannabis; Cell culture; Cell death; Cell Line, Tumor; Cell lines; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Cytotoxicity; Experiments; HCT116 Cells; Humans; Immunoglobulins; Kinases; Marijuana extract; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; Signal transduction; Signal Transduction - drug effects; siRNA; United States > US; Marijuana extract; Colon cancer; Apoptotic cell death; Bcl-2 protein family; ROS
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2019.01.011

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.
[Display omitted]
•Our results strongly suggest, for the first time, that CBD can cause Noxa-induced cell death.•CBD induced apoptotic cell death via ROS/Endoplasmic Reticulum stress-regulated Noxa activation in colorectal cancer cells.•These results suggest that CBD has important implications for the potential treatment of human CRC.