Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells
Journal
Journal of Receptors and Signal Transduction
Journal Volume
26
Journal Issue
3
Pages
199-212
Date Issued
2006
Author(s)
Cheng H.H.
Huang C.J.
Chen W.C.
Chen I.S.
Liu S.I.
Hsu S.S.
Chang H.T.
Wang J.K.
Lu Y.C.
Chou C.T.
Jan C.R.
Abstract
The effect of the carcinogen safrole on intracellular Ca2+ mobilization and on viability of human PC3 prostate cancer cells was examined. Cytosolic free Ca2+ levels ([Ca2+]i) were measured by using fura-2 as a probe. Safrole at concentrations above 10 μM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 350 μM. The Ca2+ signal was reduced by more than half after removing extracellular Ca2+ but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem, or verapamil. In Ca2+-free medium, after treatment with 650 μM safrole, 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release Ca2+. Neither inhibition of phospholipase C with U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 0.65-65 μM safrole did not affect cell viability, but incubation with 325-625 μM safrole decreased viability. Collectively, the data suggest that in PC3 cells, safrole induced a [Ca 2+]i increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion, and by inducing Ca2+ influx. Safrole can decrease cell viability in a concentration-dependent manner. Copyright ? Taylor & Francis Group, LLC.
Subjects
Ca2+; Fura-2; PC3 cells; Prostate; Safrole
SDGs
Other Subjects
1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione; adenosine triphosphatase (calcium); calcium ion; carcinogen; diltiazem; fura 2; nicardipine; nifedipine; nimodipine; phospholipase C; protein kinase C; safrole; thapsigargin; verapamil; calcium channel blocking agent; phospholipase C; protein kinase C; article; calcium mobilization; calcium signaling; cancer cell; cell viability; concentration (parameters); controlled study; cytosol; cytotoxicity; endoplasmic reticulum; enzyme activity; enzyme inhibition; extracellular calcium; human; human cell; male; prostate cancer; calcium signaling; cell survival; drug effect; metabolism; pathology; prostate tumor; tumor cell line; Calcium Channel Blockers; Calcium Signaling; Carcinogens; Cell Line, Tumor; Cell Survival; Humans; Male; Phospholipase C; Prostatic Neoplasms; Protein Kinase C; Safrole
Type
journal article