Apoptotic, necrotic, and antiproliferative activity of diosgenin and diosgenin glycosides on cervical cancer cells

Abstract (25R)-spirost-5-en-3β-ol, also known as diosgenin (DSG), exerts antiproliferative activity on diverse cell lines, induces apoptosis, and acts as a chemopreventative agent. However, the relationship between DSG glycosides and apoptotic, necrotic, and antiproliferative activity remains unclear. It is in this regard that we report the antiproliferative, necrotic, and apoptotic activities of DSG and its glycoside derivatives: (25R)-spirost-5-en-3β-yl O-β-D-glucopyranoside (3GD), (25R)-spirost-5-en-3β-yl O-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranoside (3GRD); and (25R)-spirost-5-en-3β-yl O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-D-glucopyranoside), also known as dioscin (DSC), in in vitro assays of cervical HeLa and CaSki cancer cells. The results demonstrated that DSG glycosidic derivatives preserved their antiproliferative activity. However, in both cancer cell lines, 3GD and 3GRD were less potent than DSG, while DSC was more potent than DSG. With respect to necrotic activity, all tested compounds showed no or low activity on the two cervical cancer cell lines. Regarding apoptosis, the results showed that DSG glycosides were better apoptosis-inducers than DSG, suggesting that glucose and rhamnose residues play a central role in enhancing the apoptotic activity of DSG. Finally, DSG and its glycosidic derivatives were shown to affect the proliferative potential of lymphocytes (non-tumour cells) to a lesser extent than cancer cells, suggesting that these compounds have selective action. In conclusion, the results indicate that DSG and its glycosidic derivatives are promising anticancer compounds since they are compounds with low necrotic activity and selective action.