title: 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 IC (50) values ranging from 1.72 to 11.02 microM against CCRF-CEM and 2.09 to 13.56 microM 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. BBB:blood-brain barrier CNS:central nervous system p-gp:P-glycoprotein PBCEC:porcine brain capillary cells.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Adams
authors.forename: Anne
authors.initials: A
authors.lastname: Mahringer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Gert
authors.initials: G
authors.lastname: Fricker
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D011564:Furocoumarins / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D015394:Molecular Structure; D027821:Rutaceae / Q000737:chemistry*; D013552:Swine
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D011564:Furocoumarins