Effects of trapidil and suramin on growth factor-induced calcium response and tyrosine phosphorylation in human glioma cells.
Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce the proliferation of glioma cells in vitro. Trapidil and suramin inhibit this growth factor-stimulated glioma cell growth, but the mechanisms are not fully understood. The effects of trapidil and suramin on PDGF- and EGF-induced early biochemical events in T98G cells were studied. PDGF induced a rapid increase of intracellular free calcium concentration ([Ca2+]i) in fura-2/acetoxymethyl ester-loaded single glioma (T98G) cells. This increase was completely inhibited by removal of extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)-N,N,N,N-tetraacetic acid but not by an L-type calcium channel blocker (nicardipine), suggesting that PDGF may cause calcium influx through voltage-independent calcium channels in T98G cells. Trapidil and suramin blocked the PDGF-induced calcium response and inhibited the PDGF-initiated tyrosine phosphorylation of the PDGF receptor as detected by Western blot analysis using an antibody specific for phosphotyrosine. Trapidil and suramin also inhibited EGF-initiated calcium response in T98G cells, but only partially inhibited EGF-initiated tyrosine phosphorylation at the same concentrations. Our results suggest that trapidil and suramin inhibit PDGF- and EGF-initiated early biochemical events, and thus suppress growth factor-induced cell proliferation.
Bando
K
K
Department of Neurosurgery, School of Medicine, University of Tokushima, Japan.
Kannuki
S
S
Rokutan
K
K
Shouno
M
M
Matsumoto
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology*; D014192:Trapidil / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D013498:Suramin; D004815:Epidermal Growth Factor; D014192:Trapidil; D002118:Calcium