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Cell Death Dis ; 10(11): 846, 2019 11 07.
Article in English | MEDLINE | ID: mdl-31699976

ABSTRACT

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.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis , Biomarkers, Tumor/metabolism , Cannabidiol/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Mitochondrial Proteins/metabolism , Stomach Neoplasms/pathology , X-Linked Inhibitor of Apoptosis Protein/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Biomarkers, Tumor/genetics , Cell Proliferation , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Mitochondrial Proteins/genetics , Neoplasm Invasiveness , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Tumor Cells, Cultured , X-Linked Inhibitor of Apoptosis Protein/genetics , Xenograft Model Antitumor Assays
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