The effect of green tea catechins on breast cancer resistance protein activity and intestinal efflux of aflatoxin B1 via breast cancer resistance protein in Caco-2 cells

Aflatoxin B-1 (AFB(1)), a mycotoxin produced by Aspergillus spp., was proved as one of the major causes of human hepatocellular carcinoma (HCC) when chronically consumed. An efflux of AFB(1) was reported to be associated with breast cancer resistance protein (BCRP) whose activity could also be modulated by green tea catechins. The purpose of this study was, therefore, to examine the impacts of green tea catechins on BCRP activity in Caco-2 cells by H33342 (bis-benzamide, BCRP substrate) accumulation and AFB(1) efflux. Results showed a significant decrease (p < 0.05) of AFB(1) in the efflux ratio following the incubation with Ko143, a specific BCRP inhibitor, and sodium fluoride, confirming the association of BCRP in AFB(1) efflux transport across the cells. Pre-incubation with green tea and gallate catechins (ECG and EGCG) significantly reduced the efflux ratio of AFB(1) (p < 0.05) and significantly increased the intracellular H33342 substrate (p < 0.05) in Caco-2 cells, clearly indicating the inhibitory effects of green tea and gallate catechins on BCRP function. Further study on H33342 accumulation revealed a dose-dependent increment of intracellular H33342 when co-administered with increasing concentrations of AFB(1). This result implied a possible role of AFB(1) as a BCRP competitive inhibitor. The findings from this study concluded the roles of BCRP as an efflux transporter for AFB(1) and could be modulated by the exposure of green tea catechins. Owing to a reduction of its efflux, an inhibitory effect of BCRP when pre-exposed with green tea catechins could be crucial for AFB(1) cellular accumulation.