Statins as inhibitors of voltage-gated potassium channels Kv1.3 in cancer cells

Abstract

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Factors for COVID-19 Infection that Govern the Severity of Illness

“…Cinnamaldehyde, cinnamyl acetate, these two phenyl terpenoids have been found to show high chemical reactivity with a molecular dipole moment of 4.53 Debye and lower electronegativity of -4.34 that signifies its capability of inhibition [179]. Resveratol found in grape skin along with piceatannol found in berries, grapes are stilbenoids which are a class of phenolic compounds found in grape skin formed a stable complex with the amino acid residues of the S protein ACE2 Receptor complex via hydrophobic, hydrogen and ionic interactions [180,181]. Taraxerol, Friedlin, Stigmasterol isolated from a perennial herb Clerodendrum spp.…”

Co-Application of Statin and Flavonoids as an Effective Strategy to Reduce the Activity of Voltage-Gated Potassium Channels Kv1.3 and Induce Apoptosis in Human Leukemic T Cell Line Jurkat

“…Figure 1 A depicts whole-cell currents recorded in a Jurkat T cell applying a “voltage ramp” (see Materials and Methods) under control conditions, upon a co-application of simvastatin and mevastatin at the concentration of 6.0 μM, and after wash-out of the compounds. The concentration of 6.0 μM was chosen because it was shown that the statins applied at this concentration significantly and reversibly inhibited whole-ell Kv1.3 currents in Jurkat T cells [ 12 ].…”

“…It is known that the inhibitory effects of both studied statins are accompanied by a significant acceleration of the inactivation rate of Kv1.3 currents by means of a significant reduction in the inactivation time constant [ 12 ]. Therefore, it was of interest to prove whether a co-application of simvastatin and mevastatin could further influence the inactivation rate of the currents.…”

“…Recently published results showed that the ability to inhibit Kv1.3 channels is shared by three plant-derived statins: pravastatin, mevastatin, and simvastatin [ 12 ]. Statins are organic compounds that are applied in the treatment of hypercholesterolemia and atherosclerosis [ 13 ] and might also be key therapeutic agents in the therapy of severe COVID-19 cases [ 14 ].…”

“…Moreover, the statins evastatin and simvastatin exert antiproliferative, pro-apoptotic, and drug-resistance reversal effects in Kv1.3 channel-expressing human colon adenocarcinoma cell line LoVo and its doxorubicin-resistant subline LoVo/Dx [ 15 ]. Interestingly, the inhibitory effect of simvastatin and mevastatin on Kv1.3 channels resembles the effect exerted on the channels by the flavonoids 8-prenylnaringenin (8-PN), acacetin, and chrysin [ 10 , 12 ]. This may indicate that the inhibitory effects exerted on Kv1.3 channels by statins and flavonoids are additive.…”