The investigation of minoxidil-induced [Ca2+]irises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells.
Minoxidil is clinically used to prevent hair loss. However, its effect on Ca2+homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca2+levels ([Ca2+]i) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca2+]irises in a concentration-dependent manner. This Ca2+signal was inhibited by 60% by removal of extracellular Ca2+. Minoxidil-induced Ca2+influx was confirmed by Mn2+-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 Ca2+signal in Ca2+containing medium by 60%. Treatment with the endoplasmic reticulum Ca2+pump inhibitor 2,5-ditert-butylhydroquinone (BHQ) in Ca2+-free medium abolished minoxidil-induced [Ca2+]irises. Conversely, treatment with minoxidil abolished BHQ-induced [Ca2+]irises. Inhibition of phospholipase C (PLC) with U73122 abolished minoxidil-evoked [Ca2+]irises. Overnight treatment with minoxidil killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelation of cytosolic Ca2+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 [Ca2+]irises that involved Ca2+entry through PKC-regulated store-operated Ca2+channels and PLC-dependent Ca2+release from the endoplasmic reticulum. Minoxidil-induced cytotoxicity in a Ca2+-independent manner.
a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
I-Shu
IS
Chen
b Department of Nursing , Division of Basic Medical Sciences, Chang Gung University of Science and Technology , Chia-Yi , Taiwan.|c Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology , Chia-Yi , Taiwan.
Chiang-Ting
CT
Chou
a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Yuan-Yuarn
YY
Liu
a Department of Surgery , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Chia-Cheng
CC
Yu
d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Wei-Zhe
WZ
Liang
e Department of Nursing , Tzu Hui Institute of Technology , Pingtung , Taiwan , and.
Chun-Chi
CC
Kuo
f Department of Pharmacy , Tajen University , Pingtung , Taiwan.
Pochuen
P
Shieh
f Department of Pharmacy , Tajen University , Pingtung , Taiwan.
Daih-Huang
DH
Kuo
f Department of Pharmacy , Tajen University , Pingtung , Taiwan.
Fu-An
FA
Chen
d Department of Medical Education and Research , Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.
Chung-Ren
CR
Jan
D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000959:Antihypertensive Agents; D008914:Minoxidil; D002118:Calcium
Ca2+; endoplasmic reticulum; human prostate cancer cells; minoxidil