Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells.
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 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 350 microM. 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 microM safrole, 1 microM 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 microM safrole did not affect cell viability, but incubation with 325-625 microM safrole decreased viability. Collectively, the data suggest that in PC3 cells, safrole induced a [Ca2+]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.
Chang
H C
HC
Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Cheng
H H
HH
Huang
C J
CJ
Chen
W C
WC
Chen
I S
IS
Liu
S I
SI
Hsu
S S
SS
Chang
H T
HT
Wang
J K
JK
Lu
Y C
YC
Chou
C T
CT
Jan
C R
CR
D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D012451:Safrole / Q000633:toxicity*; D010738:Type C Phospholipases / Q000378:metabolism
D002121:Calcium Channel Blockers; D002273:Carcinogens; D011493:Protein Kinase C; D010738:Type C Phospholipases; D012451:Safrole