Biochemistry and Cell Biology - ۲۰۱۴

We investigated the cytotoxic activities of crocin and crocetin, ۲ major carotenoids isolated from the stigma of Crocus sativus (saffron), on ۵ human cancer cell lines and proposed their possible anticancer mechanisms. Crocetin, a glycosylated carotenoid, showed approximately ۵- to ۱۸-fold higher cytotoxicity than crocin, a carboxylic carotenoid (IC۵۰ of ۰.۱۶-۰.۶۱ mmol/L for crocetin vs. ۲.۰-۵.۵ mmol/L for crocin). This suggests that structural differences account for the different efficacies between them. Fluorescence-activated cell sorting (FACS) analysis showed that crocetin induced a significant level of cellular reactive oxygen species (ROS) in HeLa cells, whereas crocin did not. This ROS induction supported the cytotoxicity of crocetin, but not of crocin. A significant activation of nuclear factor erythroid ۲-related factor ۲ (Nrf۲) was observed in both HeLa cells treated with crocin and crocetin: a ۳.۰-fold increase by ۱ mmol/L crocetin and a ۱.۶-fold increase by ۰.۸ mmol/L crocin compared to the control. Furthermore, both crocetin and crocin reduced the protein expression of lactate dehydrogenase A (LDHA), one of the targets for chemoprevention in cancer cells, by ۳۴.۲% and ۱۰.۵%, respectively, compared to the control in HeLa cells. These findings suggest that crocetin and crocin have different mechanisms for their observed cytotoxicity in cancer cell lines