The Influence of 6-Prenylnaringenin and Selected Non-prenylated Flavonoids on the Activity of Kv1.3 Channels in Human Jurkat T Cells.

ABSTRACT

The influence of a prenylated flavonoid-6-prenylnaringenin (6-PR) and selected non-prenylated flavonoids acacetin, chrysin, baicalein, wogonin, and luteolin on the activity of voltage-gated potassium channels Kv1.3 was investigated in human leukemic Jurkat T cells. Electrophysiological measurements were accompanied by studies on the cytotoxic effect of the examined compounds on Jurkat T cells. Electrophysiological studies were performed using the whole-cell patch-clamp technique. Cell viability was determined using the MTT assay. 6-PR inhibited Kv1.3 channels in Jurkat T cells in a concentration-dependent manner. The estimated value of the half-blocking concentration (EC50) was about 5.76 µM. Among non-prenylated flavonoids, acacetin and chrysin inhibited Kv1.3 channels in Jurkat T cells when applied at the concentration of 30 µM, whereas baicalein, wogonin, and luteolin were ineffective at this concentration. The inhibitory effects of acacetin and chrysin on Kv1.3 channels were significantly less potent than the inhibition caused by 6-PR. All tested compounds inhibited growth of Jurkat T cells in a concentration-dependent manner. Wogonin and chrysin were the most cytotoxic flavonoids tested, whereas baicalein and 6-PR were the least cytotoxic compounds. In accordance to our hypothesis the prenylated flavonoid (6-PR) was much more effective inhibitor of Kv1.3 channels than non-prenylated compounds selected for this study. The inhibition of Kv1.3 channels by 6-PR, acacetin, and chrysin was not related to cytotoxicity of these compounds. The channels' inhibition might be involved in anti-proliferative and pro-apoptotic effects of 6-PR, acacetin and chrysin observed in cancer cell lines expressing these channels.