Genistein and Resveratrol: Inhibitors of Kv1.3 Channels in Cancer Cells

Background: genistein and resveratrol are bioactive compounds isolated from plants, recognised for their diverse biological activities including anti-cancer properties. Both compounds are also known as modulators of potassium channels, including the Kv1.3 ones. These channels are expressed in both normal and cancerous tissues. Their activity is crucial in regulating cell proliferation and apoptosis in cells that express Kv1.3 channels. The potential clinical application of channel inhibitors may extend to treating cancers characterized by an over expression of Kv1.3 channels. Methods: this study investigates the inhibitory effects of genistein and resveratrol on Kv1.3 channels in cancer cells – human leukemic Jurkat T cells, applying the whole-cell patch-clamp technique. Results: applying both compounds at concentrations ranging from 3 μM to 90 μM leads to a dose-dependent inhibition of the channel activity, reducing it to approximately 50% of control level. This inhibitory effect was reversible and associated with a significant reduction of the activation rate. When combined with simvastatin, the inhibitory effect exhibited synergy; however, it was additive when co-applied with mevastatin. Conclusion: the inhibition of Kv1.3 channels is likely linked to the anti-cancer activities of these compounds on Kv1.3 channel- expressing cancer cells, especially when co-applied with the statins.