title: In vitro cytotoxic and anticlastogenic activities of saxifragifolin B and cyclamin isolated from Cyclamen persicum and Cyclamen libanoticum.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Laboratoire de Pharmacognosie et Ethnopharmacologie, UMR MD3, Faculté de Pharmacie, Aix-Marseille Université , Marseille Cedex , France .
authors.forename: Leina
authors.initials: L
authors.lastname: El Hosry
authors.forename: Carole
authors.initials: C
authors.lastname: Di Giorgio
authors.forename: Caroline
authors.initials: C
authors.lastname: Birer
authors.forename: Jean
authors.initials: J
authors.lastname: Habib
authors.forename: Marie
authors.initials: M
authors.lastname: Tueni
authors.forename: Sok-Siya
authors.initials: SS
authors.lastname: Bun
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Herbette
authors.forename: Michel
authors.initials: M
authors.lastname: De Meo
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ollivier
authors.forename: Riad
authors.initials: R
authors.lastname: Elias
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity; D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D003412:Cricetulus; D031824:Cyclamen / Q000737:chemistry*; D006801:Humans; D015162:Micronucleus Tests; D016685:Mitomycin / Q000494:pharmacology / Q000633:toxicity; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000903:Antibiotics, Antineoplastic; D016587:Antimutagenic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D012503:Saponins; D014315:Triterpenes; C000593211:cyclamin; C523878:saxifragifolin B; D016685:Mitomycin
keywords: Antioxidant; Primulaceae; chemopreventive; micronucleus assay