Effect of Flavonoids on Glutathione Level, Lipid Peroxidation and Cytochrome P450 CYP1A1 Expression in Human Laryngeal Carcinoma Cell Lines
Ksenija Durgo1*, Lidija Vuković2, Gordana Rusak3, Maja Osmak2 and Jasna Franekić Čolić1
1Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, HR-10 000 Zagreb, Croatia
2Ruđer Bošković Institute, Bijenička 54, HR-10 000 Zagreb, Croatia
3Faculty of Science, University of Zagreb, Rooseveltov trg 6, HR-10 000 Zagreb, Croatia
Article history:
Received November 4, 2005
Accepted June 29, 2006
Key words:
flavonoids, tumor cells, cytotoxicity, glutathione, lipid peroxidation, cytochrome 1A1
Summary:
Flavonoids are phytochemicals exhibiting a wide range of biological activities, among which are antioxidant activity, the ability to modulate activity of several enzymes or cell receptors and possibility to interfere with essential biochemical pathways. Using human laryngeal carcinoma HEp2 cells and their drug-resistant CK2 subline, we examined the effect of five flavonoids, three structurally related flavons (quercetin, fisetin, and myricetin), one flavonol (luteolin) and one glycosilated flavanone (naringin) for: (i) their ability to inhibit mitochondrial dehydrogenases as an indicator of cytotoxic effect, (ii) their influence on glutathione level, (iii) antioxidant/prooxidant effects and influence on cell membrane permeability, and (iv) effect on expression of cytochrome CYP1A1. Cytotoxic action of the investigated flavonoids after 72 hours of treatment follows this order: luteolin>quercetin>fisetin>naringin>myricetin. Our results show that CK2 were more resistant to toxic concentrations of flavonoids as compared to parental cells. Quercetin increased the total GSH level in both cell lines. CK2 cells are less perceptible to lipid peroxidation and damage caused by free radicals. Quercetin showed prooxidant effect in both cell lines, luteolin only in HEp2 cells, whereas other tested flavonoids did not cause lipid peroxidation in the tested cell lines. These data suggest that the same compound, quercetin, can act as a prooxidant, but also, it may prevent damage in cells caused by free radicals, due to the induction of GSH, by forming less harmful complex. Quercetin treatment damaged cell membranes in both cell lines. Fisetin caused higher cell membrane permeability only in HEp2 cells. However, these two compounds did not enhance the damage caused by hydrogen peroxide. Quercetin, naringin, myricetin and fisetin increased the expression of CYP1A1 in both cell lines, while luteolin decreased basal level of CYP1A1 only in HEp2 cells. In conclusion, small differences in chemical structure of flavonoids led to drastic change of their biological effects.
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