TY - JOUR ID - 89925 TI - Licochalcone A Induces Cholangiocarcinoma Cell Death Via Suppression of Nrf2 and NF-κB Signaling Pathways JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Laphanuwat, Phatthamon AU - Kongpetch, Sarinya AU - Senggunprai, Laddawan AU - Prawan, Auemduan AU - Kukongviriyapan, Veerapol AD - Department of Pharmacology, Faculty of Medicine and Cholangiocarcinoma Research Institute, Khon Kaen University, 40002, Thailand. Y1 - 2022 PY - 2022 VL - 23 IS - 1 SP - 115 EP - 123 KW - cholangiocarcinoma KW - licochalcone A KW - anti-cancer KW - reactive oxygen species KW - Anti-migration DO - 10.31557/APJCP.2022.23.1.115 N2 - Objective: To investigate the anti-tumor effect of licochalcone A (LCA) on proliferation and migration in cholangiocarcinoma (CCA) cells and to elucidate their underlying mechanisms. Methods: Human CCA cells, KKU-100, KKU-213, KKU-214, KKU-156, and KKU-452 were used to study effect of LCA on proliferation and migration by a cytotoxicity assay, wound healing assay. Reactive oxygen species levels were evaluated using DHE-fluorescent probes. Proteins associated with cancer survival and progression were analyzed by immune blotting assay. Results: LCA suppressed proliferation and induced cell death in CCA cells including KKU-100, KKU-213, KKU-214, KKU-156, and KKU-452. The CCAs cells were suppressed in association with LCA-induced accumulation of intracellular reactive oxygen species (ROS). Increased formation of ROS was causally related with suppression of Nrf2 and its down-stream antioxidant and cytoprotective enzymes. These effects may lead to the expression of Bax and release of cytochrome c and ensuring cell death.  Interestingly, LCA could also inhibit cell migration and cell cycle arrest at low concentrations. These effects were associated with down-regulation of NF-kB, STAT3 and their down-stream proteins, cyclin D1, VEGF, and ICAM-1. Conclusions: These results suggest that LCA has potential therapeutic activity in suppression of CCA cells. UR - https://journal.waocp.org/article_89925.html L1 - https://journal.waocp.org/article_89925_6c9978beff172acede5db1cb1e98f8a7.pdf ER -