AI Article Synopsis
- Cannabidiol (CBD) enhances the effectiveness of cabozantinib, a drug used to treat advanced liver cancer (hepatocellular carcinoma), by increasing cancer cell death and triggering apoptosis.
- The therapeutic effects of this combination treatment are linked to the activation of p53 through endoplasmic reticulum (ER) stress rather than typical cannabinoid receptor signaling.
- Inhibition of p53 or ER stress reduces the cancer-fighting effects of the treatment, indicating their crucial role in this combination therapy's success against HCC.
Article Abstract
Cannabidiol (CBD), a primary constituent in hemp and cannabis, exerts broad pharmacological effects against various diseases, including cancer. Additionally, cabozantinib, a potent multi-kinase inhibitor, has been approved for treating patients with advanced hepatocellular carcinoma (HCC). Recently, there has been an increase in research on combination therapy using cabozantinib to improve efficacy and safety when treating patients. Here, we investigated the effect of a combination treatment of cabozantinib and CBD on HCC cells. CBD treatment enhanced the sensitivity of HCC cells to cabozantinib-mediated anti-cancer activity by increasing cytotoxicity and apoptosis. Phospho-kinase array analysis demonstrated that the apoptotic effect of the combination treatment was mainly related to p53 phosphorylation regulated by endoplasmic reticulum (ER) stress when compared to other kinases. The inhibition of p53 expression and ER stress suppressed the apoptotic effect of the combination treatment, revealing no changes in the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-8, or cleaved caspase-9. Notably, the effect of the combination treatment was not associated with cannabinoid receptor 1 (CNR1) and the CNR2 signaling pathways. Our findings suggest that the combination therapy of cabozantinib and CBD provides therapeutic efficacy against HCC.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10417827 | PMC |
| http://dx.doi.org/10.3390/cancers15153987 | DOI Listing |
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