Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 47Nga Ting Colette Chiu 1 , Emma Tomlinson Guns 2 , William Jia 31Department of Pathology and Laboratory Medicine,UBC, 2 Department of Urologic Sciences,UBC, 3 Department of SurgeryNga Ting Colette Chiu20(s)-protopanaxatriol affects the expression ofcytochrome p450 3a4Backround/ObjectivesAlthough ginseng and its active ingredients, ginsenosides, are used extensively as complementary and alternativemedicines, their effects on the metabolism of concurrently used drugs are yet to be determined. Prolonged use ofan herb may lead to changes in the expression of drug metabolising enzymes leading to clinicially significant herbdrug interaction. Cytochrome P450 3A4 (CYP3A4) is one such enzymes that is responsible for the metabolism ofmore than 50% of orally taken xenobiotics. We hypothesize that dietary intake of ginsenoside metabolites, 20(S)protopanaxatriol (aPPT), cause a change in the bioavailability of concurrently used drugs by altering the geneexpression and enzymatic activities of CYP3A4. Specifically, the effect of aPPT on CYP3A4 gene expression andenzymatic activities in combination with 1,25- dihydroxyvitamin D3 (VD) in LS174T cells will be determined.MethodsLS174T cells was treated simultaneously with or without 0.1nM or 1nM of VD and different concentration (0, 0.001,0.01, 0.1, 1, 10, 50, and 100μM) of aPPT. Cell viability was determined by MTT assay. CYP3A4 protein expressionwas determined by western blotting. Total ginsenosides, Rg1, aPPD, and aPPT were tested for their abilities to inhibitCYP3A4 enzymatic activities in vitro using dibenzylfluorescein as a probe.Results and ConclusionsaPPT (up to 10μM) alone or in combination with VD is not cytotoxic to LS174T cells. aPPT induces CYP3A4protein expression with 0.1nM VD in a concentration dependent manner in LS174T cells. However, aPPT inhibitsrecombinant CYP3A4 enzymatic activities with IC50 of 2.35μM.58 2 0 1 0 * P o s t e r P r e s e n t a t i o n s