Title | 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-kappa B signaling pathway |
Authors | Zheng, Tingting Xiao, Haitao Shen, Yuehong Zhang, Xue Jiang, Kunkun Liu, Li Bai, Xiaohe Peng, Jiao Chen, Yun |
Affiliation | Peking Univ, Shenzhen Hosp, Dept Ultrasound, Shenzhen 518036, Guangdong, Peoples R China Shenzhen PKU HKUST Med Ctr, Biomed Res Inst, Shenzhen Key Lab Drug Addict & Medicat Safety, Shenzhen 518036, Guangdong, Peoples R China Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518061, Guangdong, Peoples R China Peking Univ, Dept Stomatol, Shenzhen Hosp, Shenzhen 518061, Guangdong, Peoples R China Harbin Inst Technol Shenzhen, Sch Mat Sci & Engn, Shenzhen 518055, Guangdong, Peoples R China Peking Univ, Dept Pharm, Shenzhen Hosp, Shenzhen 518036, Guangdong, Peoples R China |
Keywords | curzerenone apoptosis ROS lung cancer Bax Bcl-2 |
Issue Date | 2019 |
Publisher | JOURNAL OF BUON |
Abstract | 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-kappa B 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 mu M. The anticancer effects of curzerenone were due to the induction of apoptosis which was also associated with alteration of apoptosisrelated 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-kappa B 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. |
URI | http://hdl.handle.net/20.500.11897/548517 |
ISSN | 1107-0625 |
Indexed | SCI(E) |
Appears in Collections: | 深圳医院 |