HONG-CHIANG CHANGCheng 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.2021-01-262021-01-2620061079-9893https://www.scopus.com/inward/record.uri?eid=2-s2.0-33646556095&doi=10.1080%2f10799890600662595&partnerID=40&md5=d79758b7936440cb9207037a7784c811https://scholars.lib.ntu.edu.tw/handle/123456789/541999The 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.Ca2+; Fura-2; PC3 cells; Prostate; Safrole[SDGs]SDG31 [[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; Safrolejournal article10.1080/10799890600662595167777152-s2.0-33646556095