Calcium-dependence of hydrogen peroxide-induced c-fos expression and growth stimulation of multicellular prostate tumor spheroids.
Hydrogen peroxide (H2O2) in nanomolar concentrations (20-100 nM) stimulated the growth of small (diameter 100 +/- 30 microm) multicellular prostate cancer spheroids and increased c-fos expression. H2O2 transiently raised [Ca2+]i by Ca2+ release from intracellular stores as the transient persisted in low (10 nM) Ca2+ solution but was abolished when intracellular Ca2+ stores were depleted by thapsigargin or chelation of [Ca2+]i with BAPTA. The H2O2-induced [Ca2+]i transient was furthermore inhibited by the P2-purinoreceptor antagonists suramin and basilen blue, indicating that H2O2 may act via purinergic receptor stimulation. Treatment of spheroids with either suramin, basilen blue or BAPTA inhibited the H2O2-induced growth stimulation and c-fos expression, indicating that the H2O2-mediated growth stimulation of multicellular spheroids is mediated via a Ca2+-dependent pathway.
Sauer
H
H
Institute for Neurophysiologie, University of Cologne, Germany. hs@physiologie.uni-koeln.de
Diedershagen
H
H
Hescheler
J
J
Wartenberg
M
M
D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002118:Calcium