CaV1.3 Ion channel expression and hormone therapy in prostate cancer

CaV1.3 was overexpressed in AR-positive PCa cells but appeared to be localised within subcellular compartments. Treatment of LNCaP cells with AR antagonist, Enzalutamide resulted in the re-localisation of CaV1.3 to the plasma membrane where calcium imaging techniques highlighted the presence of depolarisation-induced calcium responses in a subpopulation of cells. Nifedipine-induced inhibition of CaV1.3 in ENZ-treated LNCaP cells appeared to increase apoptosis, albeit not significantly, compared to ENZ treatment alone.

Investigation of trafficking mechanisms of CaV1.3 showed that plasma membrane surface expression of these ion channels is enhanced in LNCaP cells following treatment with trafficking inhibitor, Brefeldin A and the histone deacetylase inhibitor, sodium butyrate. Overall, the results of this study show that CaV1.3 is relevant to AR-positive and androgen-sensitive PCa and is associated with neuroendocrine differentiation.

ENZ treatment promotes CaV1.3 plasma membrane localisation and functional expression in PCa subpopulations which may be worth therapeutic exploration.