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-κB signaling pathway.

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 µM. 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.