Cannabidiol exhibits potent anti-cancer activity against gemcitabine-resistant cholangiocarcinoma via ER-stress induction in vitro and in vivo

Autor: Thatsanapong Pongking, Phonpilas Thongpon, Kitti Intuyod, Sirinapha Klungsaeng, Raynoo Thanan, Apisit Chaidee, Naruechar Charoenram, Suppakrit Kongsintaweesuk, Chadamas Sakonsinsiri, Kulthida Vaeteewoottacharn, Somchai Pinlaor, Porntip Pinlaor
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Complementary Medicine and Therapies, Vol 24, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2662-7671
DOI: 10.1186/s12906-024-04610-2
Popis: Abstract Background Failure of treatment with gemcitabine in most cholangiocarcinoma (CCA) patients is due to drug resistance. The therapeutic potential of natural plant secondary compounds with minimal toxicity, such as cannabidiol (CBD), is a promising line of investigation in gemcitabine-resistant CCA. We aim to investigate the effects of CBD on gemcitabine-resistant CCA (KKU-213BGemR) cells in vitro and in vivo. Materials In vitro, cell proliferation, colony formation, apoptosis and cell cycle arrest were assessed using MTT assay, clonogenicity assay and flow cytometry. The effect of CBD on ROS production was evaluated using the DCFH-DA fluorescent probe. The mechanism exerted by CBD on ER stress-associated apoptosis was investigated by western blot analysis. A gemcitabine-resistant CCA xenograft model was also used and the expression of PCNA and CHOP were evaluated by immunohistochemical analysis. Results The IC50 values of CBD for KKU-213BGemR cells ranged from 19.66 to 21.05 µM. For a non-cancerous immortalized fibroblast cell line, relevant values were 18.29 to 19.21 µM. CBD suppressed colony formation by KKU-213BGemR cells in a dose-dependent manner in the range of 10 to 30 µM. CBD at 30 µM significantly increased apoptosis at early (16.37%) ( P = 0.0024) and late (1.8%) stages (P
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