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.
Journal of receptor and signal transduction research. 2016 Jun 16 [Epub ahead of print]
I-Shu Chen, Chiang-Ting Chou, Yuan-Yuarn Liu, Chia-Cheng Yu, Wei-Zhe Liang, Chun-Chi Kuo, Pochuen Shieh, Daih-Huang Kuo, Fu-An Chen, Chung-Ren Jan
a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan ., b Department of Nursing , Division of Basic Medical Sciences, Chang Gung University of Science and Technology , Chia-Yi , Taiwan ., a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan ., a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan ., d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan ., e Department of Nursing , Tzu Hui Institute of Technology , Pingtung , Taiwan , and., f Department of Pharmacy , Tajen University , Pingtung , Taiwan., f Department of Pharmacy , Tajen University , Pingtung , Taiwan., f Department of Pharmacy , Tajen University , Pingtung , Taiwan., d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan .