Effects of quercetin metabolites on the enhancing effect of β-carotene on DNA damage and cytochrome P1A1/2 expression in benzo[a]pyrene-exposed A549 cells

Abstract

A549 cells were pre-incubated with β-carotene (BC) alone or in combination with quercetin or three major quercetin metabolites in human plasma, quercetin 3-glucuronide (Q3G), quercetin 3'-sulphate (Q3'S) and isorhamnetin, followed by incubation with benzo[a]pyrene (BaP), to investigate the effects of these compounds on the BaP-induced harmful effects of BC. All the quercetin metabolites at 10μM inhibited BaP+BC-induced cell death. Q3'S, Q3G and isorhamnetin also significantly decreased BaP±BC-induced DNA damage by 64%, 60% and 24%, respectively. In a similar order, these compounds suppressed BaP+BC-induced cytochrome P450 (CYP)1A1/1A2 expression by 10-50%. Q3G and Q3'S significantly decreased the intracellular reactive oxygen species formation induced by BaP+BC; however, Q3G had the best effect on decreasing the loss of BC induced by Fe/NTA. The combined effects of quercetin metabolites were additive. This study indicates that quercetin metabolites decrease the BaP-induced harmful effect of β-carotene in A549 cells by downregulating the expression of CYP1A1/1A2, at least in part.

Keywords: Benzo[a]pyrene; Cytochrome P450; Isorhamnetin; Quercetin-3-glucuronide; Quercetin-3′-sulphate; β-Carotene.