title: Cytoprotective effects of silymarin on epithelial cells against arsenic-induced apoptosis in contrast with quercetin cytotoxicity.
abstract: OBJECTIVE
  To establish the differential cytoprotective activity against arsenic (As) toxicity of the flavonoids silymarin (S), which is without protective effects on cancer cells, and quercetin (Q). Arsenic (As) has a paradoxical biomedical role: it causes oxidative damage to normal cells leading to death or malignant transformation, but can be used, for the same reason, as an anticancer pro-apoptotic agent at high doses.
  
  
  METHODS
  Aqueous hydroperoxides (AHP), JNK (c-Jun N-terminal kinase) activation, caspase activity and death phenotype were assessed in CHO-K1 cells treated with As, S, Q, As+S and As+Q (p<0.05).
  
  
  RESULTS
  Q proved to be toxic and did not exert complete protection against As, and only S was able to protect cells from As-induced oxidative death, which started after 4h with caspase activation and phosphatidylserine exteriorization on the outer cellular membrane. Although both flavonoids counteracted As-induced JNK activation (an early stress response, i.e. exposure biomarker), AHP were increased by As and Q (p<0.05). Moreover, Q-treated cells triggered per se apoptosis and even necrosis. Also, the classical sequence oxidative stress-JNK activation-cell death was seen for As, but not for Q, with S stopping the sequence.
  
  
  CONCLUSIONS
  These results strongly suggest that the use of silymarin increases the possibility of designing better arsenic-based cancer chemotherapies with less toxicity to normal cells.
authors.affiliation: Cátedra de Biología Celular, Histología y Embriología, Instituto de Biología Celular, Fac. Cs. Médicas, Universidad Nacional Córdoba, Enrique Barros S/N, Córdoba, Argentina.
authors.forename: Elio A
authors.initials: EA
authors.lastname: Soria
authors.forename: Aldo R
authors.initials: AR
authors.lastname: Eynard
authors.forename: Guillermina A
authors.initials: GA
authors.lastname: Bongiovanni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology* / Q000633:toxicity; D016466:CHO Cells; D020169:Caspases / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*; D017670:Sodium Compounds / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018053:Arsenites; D020011:Protective Agents; D012838:Silymarin; D017670:Sodium Compounds; C017947:sodium arsenite; D011794:Quercetin; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases