Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells

J Recept Signal Transduct Res. 2006;26(3):199-212. doi: 10.1080/10799890600662595.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channel Blockers / pharmacology
  • Calcium Signaling / drug effects*
  • Carcinogens / toxicity
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Kinase C / metabolism
  • Safrole / toxicity*
  • Type C Phospholipases / metabolism


  • Calcium Channel Blockers
  • Carcinogens
  • Protein Kinase C
  • Type C Phospholipases
  • Safrole