Prooxidant character of flavonoid cytotoxicity: structure-activity relationships

The action of flavonoids on bovine leukemia virus-transformed lamb fibroblasts (line FLK) and HL-60 cells was accompanied by lipid peroxidation, their toxicity was partly prevented by iron chelator desferrioxamine and antioxidant N,N'-diphenyl-p-phenylene diamine. This pointed out to the involvement of oxidative stress in flavonoid cytotoxicity. The concentration of compound for 50% survival of FLK cells (cL50) did not show correlation with polarographic oxidation half-peak potential (Ep/2) and/or partition coefficient (log P) of flavonoids; however, their toxicity to HL-60 cells was described by equation log cL50 (microM) = 3.0161 + 1.1099 Ep/2 (V) - 0.3369 log P. The toxicity of quercetin was partly prevented by nontoxic concentrations of other flavonoids examined, thus pointing out to potential neutralization of quercetin cytotoxicity by intake of flavonoid mixtures.