In vitrocytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated fromCyclamen persicumandCyclamen libanoticum

Abstract

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 Fe 2+ -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.

Chemical and pharmacological characterization of aqueous and ethanolic extracts of Cyclamen hederifolium Ait. (Primulaceae) tuber

“…Some of previous studies documented that Cyclamen species may induce cell death in different tumor cell lines, although cytotoxic mechanisms have not been proposed [8,13]. Moderate cytotoxicity of C. coum was noted against cervical and lung cancer cells (HeLa and H1299, respectively) [35] .…”

“…trochopteranthum against hepatocelular (HepG2) and colorectal adenocarcinoma (Caco-2) cell lines, while C. pseudibericum exhibited activity against non-small cell lung carcinoma cells (A549) [38,39] . Although strong cytotoxic effect was oberved in investigation of C. to the extracts of these plants, since the experiments were performed with isolated and purified secondary metabolites (saponins) [8] . C. hederifolum has not been not tested Unusual effect was observed for aqueous extract in concentrations up to 15.625 μg/ml, which produced no cytotoxic activity in some cell lines at different times of incubation -HCT116 and 4T1 cell line (24h and 72h of incubation) and CT26 (at 48h and 72h) and LLC1 (24h).…”

“…There are also some reports on bioactivity of isolated compounds from the tubers of Cyclamen spp. [8,9] . However, biological activity of C. hederifolium has not been abundantly documented.…”

“…hederifolium to its content of phenols and triterpenic saponosides [8,15,16] . There are saponins in C. hederifolium that have been identified as cyclamin, deglucocyclamin, cyclaminorin, hederifoliosides A-E and ardisicrenoside D. After isolation the were investigated for inducing apoptosis, cytotoxic and hemolytic effects by the change of the cell membrane permeability and intracellular signaling pathways [8,9,[14][15][16] .…”

Cytotoxic Activity of Cyclamen Persicum Ethanolic Extract on MCF-7, PC-3 and LNCaP Cancer Cell Lines

“…The anti-oxidant properties of this species have been previously evaluated, which suggested the possibility of anti-proliferative potential for these plants (Metın et al 2013;Mazouz andDjeddi, 2014 andJaradat et al 2015). Although the cytotoxicity of C. persicum has been previously reported on breast, colon, hepatocellular carcinoma, lung, pancreatic and cervical cancer cell lines (Yildiz et al, 2013;El Hosry et al, 2014). Therefore, this plant extracts with significant cytotoxic activity should be further assessed using animal models.…”