Cytoprotective effects of silymarin on epithelial cells against arsenic-induced apoptosis in contrast with quercetin cytotoxicity.
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.
Soria
Elio A
EA
Cátedra de Biología Celular, Histología y Embriología, Instituto de Biología Celular, Fac. Cs. Médicas, Universidad Nacional Córdoba, Enrique Barros S/N, Córdoba, Argentina.
Eynard
Aldo R
AR
Bongiovanni
Guillermina A
GA
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
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