The influence of naturally occurring flavonoids, chalcones and statins on the activity of voltage-gated potassium channels Kv1.3 and viability of Kv1.3 channel-expressing cancer cells

Abstract

Voltage-gated potassium channels Kv1.3 are widely expressed in many cell types, both in the plasma membrane and in the inner mitochondrial membrane (mito Kv1.3 channels). An inhibition of the channels may putatively find clinical application in therapy of some cancers characterised by an over-expression of Kv1.3 channels, such as melanoma, pancreatic ductal adenocarcinoma (PDAC), multiple myeloma and B-type chronic lymphocytic leukaemia (B-CLL). An ability to inhibit Kv1.3 channels in cancer cells is shared by some plant-derived polycyclic compounds from the groups of flavonoids, chalcones and statins. The inhibitory effect on the channels may be significantly augmented when the flavonoids and the chalcones are co-applied with the statins: simvastatin and mevastatin. The inhibition of Kv1.3 channels, presumably mito Kv1.3 channels, may be involved in a pro-apoptotic activity of these compounds on Kv1.3 channel-expressing cancer cells. This pro-apoptotic activity may significantly be improved when the selected flavonoids and chalcones are co-applied with the statins. Therefore, these naturally occurring compounds may putatively find clinical application in therapy of above-mentioned cancers, especially when applied in a combination.