Piperine blocks voltage gated K+ current and inhibits proliferation in androgen sensitive and insensitive human prostate cancer cell lines

Piperine is an attractive therapeutic alkaloid from black pepper that exhibits a broad spectrum of pharmacological properties over various pathological disorders including cancer. Voltage gated K+ (K-V) channels play an important role in regulating cancer cell proliferation and are considered as potential target for cancer treatment. However, the implication of piperine in K-V associated anticancer activities on human prostate cancer cells LNCaP and PC-3 remains unrevealed. The electrophysiological and pharmacological data identifies that both androgen sensitive (LNCaP) and insensitive (PC-3) prostate cancer cells typically expressed voltage gated K+ current (I-K). This current was significantly blocked by piperine in a concentration-dependent manner with an IC50 value 39.91 mu M in LNCaP and 49.45 mu M in PC-3 cells. Analysis of voltage-dependence of activation kinetics showed that piperine induces a positive shift in the relative activation curve in both the cells. Piperine also depolarized the resting membrane potential by an average of 10.2 mV and 8.3 mV in LNCaP and PC-3 cells, respectively. The anticancer studies showed that, treatment with piperine concentration dependently induced G(1) phase cell cycle arrest and apoptosis in LNCaP and PC-3 cells. These results unravel that the IK inhibition might be responsible for the anticancer effect of piperine on androgen sensitive and insensitive human prostate cancer cells.