Antiovarian cancer mechanism of esculetin: inducing G0/G1 arrest and apoptosis via JAK2/STAT3 signalling pathway

Abstract Objectives Esculetin is a coumarin derivative, which is extracted from the dried barks of fraxinus chinensis Roxb. Although it is reported esculetin possesses multiple pharmacological activities, its associated regulatory mechanism on ovarian cancer isn’t well investigated. Methods Cytotoxicity is evaluated by MTT, clonogenic and living/dead cells staining assays. Migration and invasion effects are investigated by wound healing, and transwell assays. The effect of cell cycle and apoptosis are analyzed by flow cytometry and western blotting. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) is assessed by fluorescence microscope. Analysis of animal experiments are carried out by various pathological section assays. Key findings Esculetin exerts an anti- ovarian cancer effect. It is found that apoptosis induction is promoted by the accumulation of excessive ROS and inhibition of JAK2/STAT3 signalling pathway. In addition, exposure to esculetin leads to the cell viability reduction, migration and invasion capability decrease and G0/G1 phase cell cycle arrest induced by down-regulating downstream targets of STAT3. In vivo experimental results also indicate esculetin can inhibit tumour growth of mice. Conclusions Our study provides some strong evidences to support esculetin as a potential anti-cancer agent in ovarian cancer.