Prooxidant character of flavonoid cytotoxicity: Structure‐activity relationships

Abstract

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 (μM) = 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.

Relationship of Electrochemical Oxidation of Catechins on Their Antioxidant Activity in Microsomal Lipid Peroxidation.

“…This finding is consistent with what other workers have reported, in which they observed that the interaction of flavonoids with a model membrane, including their incorporation rate into cells and their orientation in a biomembrane, affected their AA or other pharmacological effects. [20][21][22][23][24] AA of Tea Extract The study of catechins is particularly important for the understanding of the antioxidant property of tea. In this paper, the AA of tea extract (mainly containing polyphenols) was tested.…”

Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

“…16) Further, it has been reported that they exert cytotoxicity at higher concentrations and in the presence of oxidation-catalyzing factors such as transition metal ions. The cytotoxicity of flavonoids toward human promyelocytic leukemia cells (HL-60), 17) human acute myelogeneous leukemia cells (KG1, KG1a, THP-1, and U937), 18) rhesus monkey kidney cells (LLC-MK2), rat glial tumor cells (C6), 19) bovine leukemia virus-transformed lamb embryo kidney fibroblasts (FLK), 20) mouse and hamster pancreatic b-cells (b TC1 and HIT), 21) human fibroblasts (HFK-2), human keratinocytes (HaCaT), human breast cancer adenocarcinoma cells (MCF-7), human neuroblastoma cells (SHEP and WAC-2), and bovine capillary endothelial cells 22) has been found. As shown above, however, there are only a few reports on the cytotoxicity of flavonoids toward human normal cells.…”

Cytocidal Effects of Polyphenolic Compounds, Alone or in Combination with, Anticancer Drugs Against Cancer Cells: Potential Future Application of the Combinatory Therapy

“…Indeed, several lines of evidence have shown that the number of hydroxyl groups on the B-ring of anthocyanidins is associated with the potency of prooxidative [45][46][47], apoptotic induction [48], anti-transformation [49], as well as antioxidative activities [1,8]. For instance, delphinidin and cyanidin that possess orthodihydroxyphenyl structure on the B-ring, showed stronger apoptotic induction in human leukemia cells [48] and inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation [49].…”