Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death Via Phosphorylation of P53 Regulated by ER Stress in Hepatocellular Carcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Aug 12

PMID 37568803

Authors

Youngsic Jeon

Taejung Kim

Hyukjoon Kwon

Jeong-Kook Kim

Young-Tae Park

Jungyeob Ham

Young-Joo Kim

Affiliations

Soon will be listed here.

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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