Chrysophanol induces cell death and inhibits invasiveness via mitochondrial calcium overload in ovarian cancer cells.

Abstract

Chrysophanol is a phytochemical typically extracted from rhubarb. Similar to other extracts from rhubarb, chrysophanol possesses anticancer activity against diverse cancerous cells. However, the apoptotic effects of chrysophanol in ovarian cancer remain unknown. In the current study, we examined the antitumorigenic activity of chrysophanol in human epithelial ovarian cancer cells, such as ES2 and OVCAR3. Chrysophanol decreased cell viability and increased cell death in a dose-dependent manner. In addition, chrysophanol markedly increased the intracellular reactive oxygen species production in ES2 cells, but only increased it slightly in OVCAR3 cells. Consistent with increased reactive oxygen species production, extensive lipid peroxidation was detected in chrysophanol-treated ES2 cells compared with that in untreated cells, whereas lipid peroxidation was unchanged in OVCAR3 cells in response to chrysophanol. Although there were no significant changes in calcium ions in the of ES2 and OVCAR3 cells, the concentration of calcium in the mitochondria increased dose dependent through disruption of the mitochondrial membrane potential in both ES2 and OVCAR3 cells compared with nontreated control cells. Moreover, chrysophanol activated the MAPK signaling pathways in the ovarian cancer cells. In addition, ovarian cancer cell invasiveness was suppressed, which implied that chrysophanol plays a role in preventing ovarian cancer metastasis. In conclusion, chrysophanol exhibits an anticancer effect via mitochondrial calcium overload and MAPK activation, suggesting its potential as a novel anticancer agent for human epithelial ovarian cancer.