In vitro Cytotoxicity and P-Glycoprotein Modulating Effects of Geranylated Furocoumarins from Tetradium daniellii

Abstract

Four antimycobacterial geranylated furocoumarins, from the fruits of Tetradium daniellii (Rutaceae), were tested in a bioassay using CCRF-CEM leukemia cells and their P-glycoprotein (p-gp) over-expressing subline CEM/ADR5000, to asses their cytotoxicity and effects on cellular efflux pumps. All showed considerable cell proliferation inhibition with IC₅₀ values ranging from 1.72 to 11.02 μM against CCRF-CEM and 2.09 to 13.56 μM against CEM/ADR5000, respectively. An assay monitoring the p-gp-dependent accumulation of a calcein fluorescent dye in porcine brain capillary endothelial cells was used to study interactions of the test substances with this efflux pump. Here, they all were shown to be only weak to moderate modulators of p-gp.

Abbreviations

BBB:blood-brain barrier

CNS:central nervous system

p-gp:P-glycoprotein

PBCEC:porcine brain capillary cells

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