Antiproliferative activities of auraptenol against drug-resistant human prostate carcinoma cells are mediated via programmed cell death, endogenous ROS production, and targeting the JNK/p38 MAPK signal pathways.

Purpose: Prostate cancer is considered to be one of the most common cancers in men and as such there is a pressing need for finding new therapeutic agents to treat this disease. Therefore, the main purpose of the current research work was to study the anticancer effects of a naturally occurring coumarin- Auraptenol- against drug-resistant human prostate cancer cells and evaluate its effects on programmed cell death, reactive oxygen species (ROS) production, and JNK/p38 MAPK signalling pathway.

Methods: Cell proliferation was examined by CCK8 cell viability assay. Apoptosis-related studies were checked by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) and Hoechst staining, as well as flow cytometry using annexin V/propidium iodide (PI) assay. Western blot was used to study the effects of Auraptenol on apoptosis-related protein expressions including Bax, Bcl-2, as well as JNK/p38 MAPK signalling pathway. ROS production was evaluated by flow cytometry.

Results: The results showed that Auraptenol caused significant reduction in the viability of the human LNCaP prostate carcinoma cells in a dose-dependent manner, exhibiting an IC50 of 25 µM in cancer cells and IC50 of 100 µM in normal PNT2 cells. The AO/EB staining assay showed that Auraptenol inhibited the viability of cancer cells via induction of apoptotic cell death, which was associated with increase in Bax and decrease in Bcl-2 levels. Hoechst staining results also confirmed that Auraptenol induced programmed cell death. The apoptotic cells increased from 0.8% in the control to 32.5% in the study group at 50 µM concentration of Auraptenol. Auraptenol also induced an increase in ROS production in a dose-dependent manner. Finally, this molecule blocked the JNK/p38 MAPK signal pathway concentration-dependently in human prostate cancer cells.

Conclusion: In conclusion, the current study indicates that this molecule could be developed as a potential anticancer drug against human prostate carcinoma provided further studies are carried out.