Cytoprotective effects of silymarin on epithelial cells against arsenic-induced apoptosis in contrast with quercetin cytotoxicity.

SORIA EA; EYNARD AR; BONGIOVANNI GA

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2010 vol. 87 p. 309 - 315

0024-3205

Aims: 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. Main 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 (pb0.05). Key findings: 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 4 h 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 (pb0.05). 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. Significance: 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.