Cytotoxic effects of S-(+)-Carvone on selected human cancer cell lines

Abstract

S-(+)-Carvone (S-CVN), the main constituent of Caraway seed (Carum carvi L.Umbelliferae), has been reported to show significant anticancer and chemopreventive effects against several cancer types. The current study aimed to evaluate the cytotoxic effects of S-CVN on four different human cancer cell lines: ovarian cancer (SW-626), triple negative breast cancer (BT-20), prostate cancer (PC-3) and lymphoma (RAJI). Using MTS proliferation assay, S-CVN showed significant concentration-dependent anti-proliferative effects against the chosen cancer cell lines, with IC50 values of 147,117,199 and 228?M in SW-626, PC-3, BT-20 and RAJI, respectively. Mechanistically, S-CVN with its ?,?-unsaturated carbonyl functionality has the potential to interact with cellular nucleophilic functional groups through Michael’s addition type of reaction. The covalent interaction may explain the observed anti-proliferative activity. To further understand the mechanism of S-CVN cytotoxicity, glutathione (GSH and GSSG) were added to SW-626 cell line as pre- and co-treatments with S-CVN. According to results, the cell viability was enhanced and the cytotoxic effect of S-CVN was extremely decreased using a range of GSH/GSSG concentrations (50 -1000?M). Moreover, the interaction between GSH and S-CVN was further confirmed by using thin layer chromatography (TLC). This is presumably attributed to the fact that the nucleophilic thiol function in GSH interacts with S-CVN ?,?-unsaturated ketone moiety at ?-C. The obtained data suggests that the reactivity of the electrophilic functionality of S-CVN plays a crucial role in its cytotoxicity.