The investigation of minoxidil-induced [Ca 2+ ] i rises and non-Ca 2+ -triggered cell death in PC3 human prostate cancer cells.

Minoxidil is clinically used to prevent hair loss. However, its effect on Ca ²⁺ homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca ²⁺ levels ([Ca ²⁺ ] _i ) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca ²⁺ ] _i rises in a concentration-dependent manner. This Ca ²⁺ signal was inhibited by 60% by removal of extracellular Ca ²⁺ . Minoxidil-induced Ca ²⁺ influx was confirmed by Mn ²⁺ -induced quench of fura-2 fluorescence. Pre-treatment with the protein kinase C (PKC) inhibitor GF109203X, PKC activator phorbol 12-myristate 13 acetate (PMA), nifedipine and SKF96365 inhibited minoxidil-induced Ca ²⁺ signal in Ca ²⁺ containing medium by 60%. Treatment with the endoplasmic reticulum Ca ²⁺ pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca ²⁺ -free medium abolished minoxidil-induced [Ca ²⁺ ] _i rises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca ²⁺ ] _i rises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca ²⁺ ] _i rises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca ²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent minoxidil's cytotoxicity. Together, in PC3 cells, minoxidil induced [Ca ²⁺ ] _i rises that involved Ca ²⁺ entry through PKC-regulated store-operated Ca ²⁺ channels and PLC-dependent Ca ²⁺ release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca ²⁺ -independent manner.