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  • Title: Quaternary benzo[c]phenathridine alkaloids sanguinarine and chelerythrine do not affect transcriptional activity of aryl hydrocarbon receptor: analyses in rat hepatoma cell line H4IIE.luc.
    Author: Dvorák Z, Sovadinová I, Bláha L, Giesy JP, Ulrichová J.
    Journal: Food Chem Toxicol; 2006 Sep; 44(9):1466-73. PubMed ID: 16782256.
    Abstract:
    Quaternary benzo[c]phenanthridine alkaloids (QBAs) sanguinarine and chelerythrine exert a plethora of biological activities. Nevertheless, the specific cellular target for these alkaloids within the cell was not identified as far. Several literary data indicate that biological effects of QBAs could be associated with aryl hydrocarbon receptor (AhR) signaling pathway, including cytochrome P450 CYP1A, however, available information are controversial. In this work we analyzed the effects of sanguinarine and chelerythrine on AhR activity in rat hepatoma cells HII4E.luc stably transfected with dioxin responsive element fused to luciferase gene (DRE-LUC). Studied QBAs were tested in submicromolar concentration range (0.0001-1 microM) and in incubation times 6, 24 and 48 h. Transcriptional activity of AhR was monitored by chemiluminiscence measurement of luciferase catalytic activity. Sanguinarine and chelerythrine did not activated AhR in any time or dose tested. Chelerythrine (1 microM) but not sanguinarine caused moderate inhibition of AhR activation by 10 picomolar dioxin (exponential phase of receptor activation). In contrast, AhR activation by 2.5 nM dioxin (saturated receptor) was not affected by either alkaloid tested. In conclusion, the findings presented here favor rather for inactivity or modest inhibitory effect of QBAs on AhR signaling pathways in vitro than for the activation of the receptor. Regarding the concentrations of QBAs occurring in vivo, the use of products containing sanguinarine and/or chelerythrine has low toxicological potential in terms of the interactions with AhR signaling pathways.
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