전영식 김태정 권혁준 김정국 Park, Young Tae Ham, Jung yeob Kim, Young Joo 2024-01-12T06:34:47Z 2024-01-12T06:34:47Z 2023-08-06 2023-08 2072-6694 https://pubs.kist.re.kr/handle/201004/79862 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. English Multidisciplinary Digital Publishing Institute (MDPI) Cannabidiol Enhances Cabozantinib-Induced Apoptotic Cell Death via Phosphorylation of p53 Regulated by ER Stress in Hepatocellular Carcinoma Article 10.3390/cancers15153987 1 Cancers, v.15, no.15 Cancers 15 15 Y scie scopus 001046186500001 Oncology Oncology Article P53-DEPENDENT APOPTOSIS IN-VITRO CANNABINOIDS GROWTH VIVO cannabidiol cabozantinib apoptosis p53 endoplasmic reticulum stress