Glutinol inhibits the proliferation of human ovarian cancer cells via PI3K/AKT signaling pathway

Purpose: To investigate the anticancer effect of glutinol on OVACAR3 human ovarian cancer cells, and to elucidate the underlying molecular mechanisms. Methods: Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle distribution, reactive oxygen species (ROS) and mitochondrial membrane potential were measured via flow cytometry, while protein expression levels were determined with western blotting assay. Results: Glutinol exerted significant growth-inhibitory effects on human OVACAR3 cells, but interestingly, it exhibited comparatively lower cytotoxic effects against normal SV40 cells. The IC50 of glutinol against human OVACAR3 cells was 6 mu M, while the IC50 against normal SV40 cells was 60 mu M. Flow cytometric analysis showed an increase in population of OVACAR3 cells in G2/M phase from 4.02 % in control to 29.05 % on treatment with 12 mu M glutinol, suggestive of G2/M phase arrest. The G2/M arrest of OVACAR3 cells was also accompanied by suppression of cyclin B1. It was also found that increases in ROS levels and decreases in MMP activities contributed to the glutinol-induced antiproliferative effects on human OVACAR3 cells. Moreover, glutinol deactivated the PI3K/AKT signaling pathway in OVACAR-3 ovarian cancer cells. Conclusion: Glutinol exerted potent anticancer effects against human ovarian cancer. Thus, it might be of potential benefit in the treatment of ovarian cancer.