PMID- 31424641 OWN - NLM STAT- MEDLINE DCOM- 20200302 LR - 20200302 IS - 2241-6293 (Electronic) IS - 1107-0625 (Linking) VI - 24 IP - 3 DP - 2019 May-Jun TI - Anticancer effects of curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-kappaB signaling pathway. PG - 907-912 AB - PURPOSE: The main objective of the current study was to examine the anticancer effects of Curzerenone - a naturally occurring sesquiterpene against gemcitabine-resistant lung carcinoma cells. The effects of Curzerenone on mitochondrial-mediated apoptosis, ROS, and ERK/MAPK and NF-kB signalling pathways were also investigated in the present study. METHODS: Cell proliferation was evaluated by MTT assay. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining as well as flow cytometry using annexin V apoptosis assay. The effects on reactive oxygen species (ROS) as well as mitochondrial membrane potential (MMP) were examined by flow cytometry. Protein expression was examined by western blotting. RESULTS: It was found that Curzerenone induced potent antiproliferative effects against the gemcitabine-resistant lung cancer cells and exhibited an IC50 of 24 microM. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosis-related proteins (Bax,Bcl-2). Curzerenone also caused ROS-mediated alterations in the MMP. Curzerenone induced cell death in gemcitabine-resistant lung cancer cells by activating p38 MAPK/ERK signalling pathway while NF-kB pathway was inhibited in a dose-dependent manner. CONCLUSIONS: In conclusion, the current results strongly indicate that Curzerenone may prove a potential anticancer drug candidate against drug-resistant lung cancer. FAU - Zheng, Tingting AU - Zheng T AD - Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China. FAU - Chen, Haitao Xiao Yuehong Shen Xue Zhang Kunkun Jiang Li Liu Xiaohe Bai Jiao Peng Yun AU - Chen HXYSXZKJLLXBJPY LA - eng PT - Journal Article PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 0 (Terpenes) SB - IM MH - Apoptosis/*drug effects MH - Cell Line, Tumor MH - Humans MH - Lung Neoplasms/*drug therapy/pathology MH - MAP Kinase Signaling System/*drug effects MH - Membrane Potential, Mitochondrial/*drug effects MH - NF-kappa B/*drug effects MH - Plant Extracts/pharmacology/*therapeutic use MH - Reactive Oxygen Species MH - Signal Transduction MH - Terpenes/pharmacology/*therapeutic use EDAT- 2019/08/20 06:00 MHDA- 2020/03/03 06:00 CRDT- 2019/08/20 06:00 PHST- 2019/08/20 06:00 [entrez] PHST- 2019/08/20 06:00 [pubmed] PHST- 2020/03/03 06:00 [medline] PST - ppublish SO - J BUON. 2019 May-Jun;24(3):907-912.