Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer

• Published in: Cell death & disease 2019-11, Vol.10 (11), p.846-13, Article 846
• Main Authors: Jeong, Soyeon, Jo, Min Jee, Yun, Hye Kyeong, Kim, Dae Yeong, Kim, Bo Ram, Kim, Jung Lim, Park, Seong Hye, Na, Yoo Jin, Jeong, Yoon A, Kim, Bu Gyeom, Ashktorab, Hassan, Smoot, Duane T., Heo, Jun Young, Han, Jeongsu, Il Lee, Sun, Do Kim, Han, Kim, Dae Hyun, Oh, Sang Cheul, Lee, Dae-Hee
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/31; 13/89; 14/19; 14/34; 38/77; 38/90; 631/67/1504/1829; 631/80/82/23; 64/60; 96/109; Animals; Antibodies; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biochemistry; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Cannabidiol - pharmacology; Cannabinoids; Cannabis; Cell Biology; Cell Culture; Cell death; Cell Proliferation; Cytosol; DIABLO protein; Female; Gastric cancer; Gene Expression Regulation, Neoplastic - drug effects; Humans; IAP protein; Immunology; Life Sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Neoplasm Invasiveness; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Therapeutic applications; Tumor Cells, Cultured; Ubiquitination; X-Linked Inhibitor of Apoptosis Protein - genetics; X-Linked Inhibitor of Apoptosis Protein - metabolism; Xenograft Model Antitumor Assays; XIAP protein
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-2001-7

According to recent studies, Cannabidiol (CBD), one of the main components of Cannabis sativa , has anticancer effects in several cancers. However, the exact mechanism of CBD action is not currently understood. Here, CBD promoted cell death in gastric cancer. We suggest that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. The expression of Smac, a known inhibitor of XIAP, was found to be elevated during CBD treatment. Moreover, CBD treatment increased the interaction between XIAP and Smac by increasing Smac release from mitochondria to the cytosol. CBD has also been shown to affect mitochondrial dysfunction. Taken together, these results suggest that CBD may have potential as a new therapeutic target in gastric cancer.