engleski

Effects of Dietary Flavonoids on Detoxyfing Cell System

Flavonoids are phytochemicals widely distributed in plants. In this work we have investigated five structurally similar flavonoids for their ability to: (i) to cause antioxidant/prooxidant effect in cells ; (ii) to change basal level of total cellular glutathione and glutathione-S-transferases ; (iii) to cause cytochrome 1A1 expression and (iv) their influence on antiapoptotic proteins expression (survivin and Bcl-2) and their ability to cause PARP degradation. For this purpose, laryngeal carcinoma cell lines HEp2 and drug resistant cell line CK2 were used. Previously, we have conclude that cell line CK2 was more resistant to cytotoxic effect of investigated flavonoids than parental, HEp2 cells. Quercetin, luteolin and fisetin have acted as prooxidants in cell lines where cytochrome 1A1 was highly expressed (cell line HEp2). Fisetin and luteolin have caused enhanced prooxidative response when cells were treated with free radicals of other origin. In cells where cytochrome 1A1 was slightly expressed, quercetin has caused protein PARP degradation and survivin expression. Luteolin has caused PARP degradation and antiapoptotic proteins expression in cells with low cytochrome 1A1 and glutathione expression. In cells where expression of cytochrome 1A1 is low and glutathione-S-transferases activity and glutathione level high, fisetin has caused PARP degradation and antiapoptotic proteins repression. These results show clear evidence of proapoptotic nature of fisetin. Naringin has shown antioxidant property, it has caused cell membrane stabilisation and higher selectivity. In cells where cytochrome 1A1 was highly expressed, together with total cellular glutathione and glutathione-S-transferases, naringin has caused Bcl-2 repression, and has shown proapoptotic action. Myricetin did not cause prooxidative damage ; it has caused expression of phase II enzymes and Bcl-2 expression, pointing its antiapoptotic nature. In conclusion, small differences in chemical structure of flavonoids lead to drastic change of their biological effects. These effects are strongly dependent of cell type as well as test systems used. Extensive studies on structure-function relationship of flavonoids in different test systems could provide rational approach to drug and chemopreventive agent design. (Supported by Croatian Ministry of science, education and sport, No. 058013).

flavonoids; detoxyfing systems phase I and II; antioxidant/prooxidant; apoptosis; laryngeal carcinoma cells

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