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Modulation of PXR and VDR Pathways by 1,25D and Bioactive Compounds of St. John's Wort and Soy in HepG2 Cells
Author(s) -
Monaco Nathan Andrew,
Renouf Mathieu,
Welsh JoEllen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a110-b
Subject(s) - pregnane x receptor , calcitriol receptor , hyperforin , nuclear receptor , chemistry , genistein , pharmacology , transactivation , hypericin , receptor , in vitro , signal transduction , hypericum perforatum , transcription factor , biochemistry , biology , endocrinology , gene
As nuclear receptor, PXR and VDR have functional similarities by altering gene transcription in response to diet‐derived ligands. Bioactive compounds of St. John's Wort and soy have been targeted as potential nuclear receptor ligands. Although PXR and drug metabolism pathways regulated by PXR (MDR‐1) have been shown to be active in liver cells, the vitamin D pathway has not been well studied in this model. Our hypothesis is that both PXR and VDR pathways are active in hepatic cells and may be modulated by bioactive compounds. We examined the in vitro effects of 24h exposure of hypericin, hyperforin, genistein and 1,25‐vitamin D 3 (1,25‐D) on HepG2 cells. Using RT‐PCR, we measured mRNA levels of nuclear receptors (PXR and VDR) and metabolic genes (MDR‐1 and CYP24). Preliminary results suggest that within 24h, cells treated with hypericin, hyperforin and genistein showed an inhibition of MDR‐1 and PXR expression compared to control (time 0). 1,25‐D induced MDR‐1 and PXR during the first 12h, followed by an inhibition between 12h and 24h. All treatments caused an inhibition of VDR and an activation of CYP24 transcripts by 24h. Taken together, these observations suggest that both PXR and VDR pathways can be modulated by bioactive compounds, indicating that they may be active in HepG2 cells. Western blot analysis is under investigation to assess gene function.