In vitro cytotoxicity and P-glycoprotein modulating effects of geranylated furocoumarins from Tetradium daniellii.
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.
Adams
Michael
M
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Graz, Austria.
Mahringer
Anne
A
Bauer
Rudolf
R
Fricker
Gert
G
Efferth
Thomas
T
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D011564:Furocoumarins