TY - JOUR

T1 - Structure-cytotoxicity relationships for dietary flavonoids

AU - Breinholt, Vibeke

AU - Dragsted, Lars Ove

N1 - (Ekstern)

PY - 1998

Y1 - 1998

N2 - The cytotoxicity of a large series of dietary flavonoids was tested in a non-tumorigenic mouse and two human cancer cell lines, using the neutral red dye exclusion assay. All compounds tested exhibited a concentration-dependent cytotoxic action in the employed cell lines. The relative cytotoxicity of the flavonoids, however, was found to vary greatly among the different cell lines. With a few exceptions, the investigated flavonoids were more cytotoxic to the human cancer cell lines, than the mouse cell line. The differences in cytotoxicity were accounted for in part by differences in cellular uptake and metabolic capacity among the different cell types. In 3T3 cells fairly consistent structure-cytotoxicity relationships were found. The most cytotoxic structures tested in 3T3 cells were flavonoids with adjacent 3',4' hydroxy groups on the B-ring, such as luteolin, quercetin, myricetin, fisetin, eriodictyol, and taxifolin. The structural requirements for cytotoxicity in the human cell lines, however, were less clear. Reduction of the cytotoxic response of the 3',4'-hydroxylated flavonoid, quercetin, by the hydroxyl radical scavenger mannitol and the metal chelator desferoxamine suggests that reactive oxygen species, produced from redox cycling of the catechol structure with molecular oxygen, is responsible in part for the cytotoxicity of this subgroup of flavonoids.

AB - The cytotoxicity of a large series of dietary flavonoids was tested in a non-tumorigenic mouse and two human cancer cell lines, using the neutral red dye exclusion assay. All compounds tested exhibited a concentration-dependent cytotoxic action in the employed cell lines. The relative cytotoxicity of the flavonoids, however, was found to vary greatly among the different cell lines. With a few exceptions, the investigated flavonoids were more cytotoxic to the human cancer cell lines, than the mouse cell line. The differences in cytotoxicity were accounted for in part by differences in cellular uptake and metabolic capacity among the different cell types. In 3T3 cells fairly consistent structure-cytotoxicity relationships were found. The most cytotoxic structures tested in 3T3 cells were flavonoids with adjacent 3',4' hydroxy groups on the B-ring, such as luteolin, quercetin, myricetin, fisetin, eriodictyol, and taxifolin. The structural requirements for cytotoxicity in the human cell lines, however, were less clear. Reduction of the cytotoxic response of the 3',4'-hydroxylated flavonoid, quercetin, by the hydroxyl radical scavenger mannitol and the metal chelator desferoxamine suggests that reactive oxygen species, produced from redox cycling of the catechol structure with molecular oxygen, is responsible in part for the cytotoxicity of this subgroup of flavonoids.

UR - http://www.scopus.com/inward/record.url?scp=0031657399&partnerID=8YFLogxK

M3 - Journal article

AN - SCOPUS:0031657399

VL - 11

SP - 193

EP - 206

JO - In Vitro and Molecular Toxicology: Journal of Basic and Applied Research

JF - In Vitro and Molecular Toxicology: Journal of Basic and Applied Research

SN - 1097-9336

IS - 2

ER -