In vitro cytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated from Cyclamen persicum and Cyclamen libanoticum

Context: The genus Cyclamen L. (Primulaceae) is rich in saponins known to have interesting biological activities. Objective: To isolate saxifragifolin B and cyclamin, two triterpene saponins, from Cyclamen libanoticum Hildebr and Cyclamen persicum Mill, and to assess their cytotoxic, clastogenic/aneugenic, and anticlastogenic effects, as well as antioxidant potential. Materials and methods: Saxifragifolin B and cyclamin were tested for their cytotoxicity against SK-BR-3, HT-29, HepG2/3A, NCI-H1299, BXPC-3, 22RV1, and normal DMEM cell lines using WST-1 assay. Their clastogenic/aneugenic activities and anticlastogenic effects against the anticancer drug mitomycin C were assessed by the in vitro micronucleus assay in CHO cells. Their antioxidant capacities were determined using Fe2+-chelating and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays. Results: Both saponins were described for the first time in Cyclamen libanoticum. They showed strong cytotoxic activities against the tested cancer cell lines. Saxifragifolin B was found to be 56-and 37-times more active than mitomycin C against breast adenocarcinoma (SK-BR-3) and lung carcinoma (NCI-H1299), respectively. Also, saxifragifolin B did not induce micronuclei formation and prevented cells from mitomycin C clastogenic effect. Cyclamin induced a significant increase of micronucleated cells after metabolic activation with S9 mix, and did not possess any anticlastogenic activity. Both molecules exhibited low antioxidant activities as compared to reference compounds. Discussion and conclusions: This study showed the remarkable cytotoxic activity of saxifragifolin B, especially against breast adenocarcinoma and lung carcinoma and its chemoprotective activity against mitomycin C. Thus, saxifragifolin B could be suggested as a potential cytotoxic drug with a preventive effect against possible exposures to genotoxic agents.