Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured MCF-7 human breast cancer cells.

摘要: The metabolism and action of trans-anethole (anethole) the estrogen-like activity compound its metabolites were studied in freshly isolated rat hepatocytes cultured MCF-7 human breast cancer cells, respectively. incubation with anethole (0.25-2.0mM) caused a concentration- time-dependent cell death accompanied by losses cellular ATP adenine nucleotide pools. Anethole at weakly toxic level (0.5mM) was metabolized to 4-methoxycinnamic acid (4MCA), 4-hydroxy-1-propenylbenzene (4OHPB), monosulfate conjugate 4OHPB; levels 4OHPB sulfate 4MCA reached approximately 20 200 microM within 2 hr, respectively, whereas that free unconjugated less than 0.5 microM. At moderately concentration (1.0mM), 10 microM, followed abrupt loss 3'-phosphoadenosine 5'-phosphosulphate (PAPS). Based on viability levels, more 4MCA. addition 2,6-dichloro-4-nitrophenol (50 microM), an inhibitor sulfotransferase, enhanced anethole-induced cytotoxicity associated ATP, PAPS, sulfate, symmetrically increased concentration. as well diethylstilbestrol (DES) bisphenol A (BPA), which are known xenoestrogenic compounds, competitively displaced 17beta-estradiol bound estrogen receptor alpha concentration-dependent manner; IC(50) values these compounds 1 x 10(-5), 10(-8) 5 10(-5)M, also (10(-8) 10(-6)M)-dependent proliferation neither nor (10(-9) 10(-5)M) affected proliferation. However, higher concentrations (>10(-4)M), rather cytotoxic. These results suggest biotransformation induces cytotoxic effect estrogenic lower cells based hydroxylated intermediate, 4OHPB.