Co-Inhibition of Kv1.3 Channel Activity by Selected Chalcones and Statins in a Model of Cancer Cell Line Jurkat T

Voltage-gated potassium channel Kv1.3 plays an important role in the regulation of survival and apoptosis in many cell types, including both normal and cancer cells. Inhibitors of these channels may potentially find clinical applications in the treatment of various diseases, including certain cancers characterized by the over-expression of Kv1.3. In this study, the effects of isobavachalcone (IBC) and two non-prenylated chalcones-2'-hydroxy-4,3'-dimethoxychalcone (HDC) and 2'-hydroxy-2-methoxychalcone (HMC)-on Kv1.3 channel activity were investigated in the Jurkat T cancer cell line using the whole-cell patch-clamp technique. The electrophysiological measurements were preceded by experiments assessing cell viability, and the patch-clamp data were consistent with results obtained from MTT-based assays. We observed an almost complete and irreversible inhibition of Kv1.3 in the presence of IBC. The non-prenylated chalcones also inhibited the channels, but with lower potency and in a reversible and incomplete manner. The inhibitory effect of IBC was significantly enhanced upon co-application with simvastatin (SIM) and mevastatin (MEV). In contrast, inhibition by the non-prenylated chalcones was significantly increased only in the presence of mevastatin, but not simvastatin. The channel inhibition may be related to the anti-proliferative and pro-apoptotic activities of these compounds in Kv1.3-expressing cancer cells. Altogether, our results indicate that both prenylated and non-prenylated chalcones, particularly in combination with statins, may represent biologically active scaffolds, warranting further optimization and preclinical evaluation.