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

Autor: I-Shu Chen, Chiang-Ting Chou, J K Wang, Hong-Chiang Chang, Shuih-Inn Liu, Hong-Tai Chang, Yih-Chau Lu, C R Jan, W. C. Chen, Chorng-Chih Huang, Shu-Shong Hsu, He-Hsiung Cheng
Rok vydání: 2006
Předmět:
Zdroj: Journal of receptor and signal transduction research. 26(3)
ISSN: 1079-9893
Popis: 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.
Databáze: OpenAIRE