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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Apoptosis*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cannabidiol / pharmacology*
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Cell Proliferation
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism*
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Neoplasm Invasiveness
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Stomach Neoplasms / genetics
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology*
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Tumor Cells, Cultured
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X-Linked Inhibitor of Apoptosis Protein / genetics
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X-Linked Inhibitor of Apoptosis Protein / metabolism*
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Xenograft Model Antitumor Assays
Substances
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Apoptosis Regulatory Proteins
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Biomarkers, Tumor
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DIABLO protein, human
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Mitochondrial Proteins
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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Cannabidiol