Effect of Triterpenoids Isolated from the Floral Spikes of Betula platyphylla var. japonica on P-Glycoprotein Function

Abstract

One of the major causes of multidrug resistance (MDR) in cancer cells is over-expression of P-glycoprotein (P-gp). We studied the effects of 20 triterpenes isolated from the floral spikes of Betula platyphylla var. japonica (B. platyphylla) on P-gp function based on our previous finding that some of them showed MDR reversing effects. We evaluated accumulations and effluxes of rhodamine 123 as a P-gp substrate with P-gp over-expressing KB-C2 cells. Among the 20 triterpenes, compounds 3, 4, 8, 9, 13, 15, and 20 increased rhodamine 123 accumulations in KB-C2 cells, and three (8, 13, and 20) of them also inhibited efflux of rhodamine 123 out of cells. In addition, compounds 13 and 20 showed a weak inhibitory activity of P-gp ATPase. These results suggested that MDR reversing effects of compounds 13 and 20 are partly involved in inhibition of P-gp ATPase.

Abbreviations

B. platyphylla:Betula platyphylla var. japonica

DMEM:Dulbecco’s modified Eagle’s medium

EDTA:ethylendiamine-N,N,N′,N′-tetraacetic acid

EGTA:O,O′-bis(2-aminoethyl)ethyleneglycol-N,N,N′,N′-tetraacetic acid

FBS:fetal bovine serum

HEPES:2-[4-(2-hydroxyethyl)-1-piperazinyl]ethane-sulfonic acid

MDR:multidrug resistance

PBS:phosphate-buffered saline

P-gp:P-glycoprotein

Tris:2-amino-2-hydroxymethyl-1,3-propanediol

Key words

Betula platyphylla var. japonica - Betulaceae - triterpenes - P-glycoprotein - KB-C2 cells

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