Inhibition of Kv1.3 Channels in Human Jurkat T Cells by Xanthohumol and Isoxanthohumol

Abstract

Using whole-cell patch-clamp technique, we investigated influence of selected compounds from groups of prenylated chalcones and flavonoids: xanthohumol and isoxanthohumol on the activity of Kv1.3 channels in human leukemic Jurkat T cells. Obtained results provide evidence that both examined compounds were inhibitors of Kv1.3 channels in these cells. The inhibitory effects occurred in a concentration-dependent manner. The estimated value of the half-blocking concentration (EC50) was about 3 μM for xanthohumol and about 7.8 μM for isoxanthohumol. The inhibition of Kv1.3 channels by examined compounds was not complete. Upon an application of the compounds at the maximal concentrations equal to 30 μM, the activity of Kv1.3 channels was inhibited to about 0.13 of the control value. The inhibitory effect was reversible. The application of xanthohumol and isoxanthohumol did not change the currents' activation and inactivation rate. These results may confirm our earlier hypothesis that the presence of a prenyl group in a molecule is a factor that facilitates the inhibition of Kv1.3 channels by compounds from the groups of flavonoids and chalcones. The inhibition of Kv1.3 channels might be involved in antiproliferative and proapoptotic effects of the compounds observed in cancer cell lines expressing these channels.

Fig. 1

Chemical structures of: xanthohumol (a) and isoxanthohumol (b)

Fig. 2

Both examined compounds reduced the intensity of the whole-cell potassium currents recorded in Jurkat T cells applying the voltage ramp protocol (shown schematically above the current records): (a) control conditions, (b) application of 15 μM of xanthohumol (left panel) and 10 μM of isoxanthohumol (right panel) and (c) “wash-out” of the examined compounds

Fig. 3

Comparison of a magnitude of the inhibition by xanthohumol (filled squares) and isoxanthohumol (empty squares) plotted as a function of logarithm of concentrations of both compounds (in μM). Data points were fitted by the Hill’s equation