Effect of triterpenoids isolated from the floral spikes of Betula platyphylla var. japonica on P-glycoprotein function.

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.