Inhibition of growth factor binding, Ca2+ signaling and cell growth by polysulfonated azo dyes related to the antitumor agent suramin.
The ability of the polysulfonated antitumor drug suramin and six related polysulfonated azo dyes to inhibit the cell growth, platelet-derived growth factor (PDGF)-receptor binding, and intracellular Ca2+ signaling of Swiss 3T3 fibroblasts was studied. Some of the azo dyes were more potent inhibitors of PDGF binding than was suramin. The concentration giving 50% inhibition (IC50) of PDGF binding was 0.5 microM for the most potent azo dye as compared with 10 microM for suramin. The azo dyes were generally more potent inhibitors of nonmitochondrial Ca2+ uptake and of inositol(1,4,5)trisphosphate-mediated Ca2+ release in permeabilized Swiss 3T3 cells than was suramin, and they were more potent inhibitors of PDGF-induced Ca2+ signaling in intact Swiss 3T3 cells. The azo dyes were only as effective as or less effective than suramin in inhibiting the growth of Swiss 3T3 cells, with IC50 values of between 74 and 361 microM being noted for the dyes as compared with 70 microM for suramin. The difference between the growth-inhibitory activity of the azo dyes and that of suramin could not be explained by metabolism of the compounds, which was not detectable in either Swiss 3T3 cells or human liver slice preparations. The results suggest that suramin and some of the azo dyes have actions on cell growth in addition to inhibition of growth factor binding and of Ca2+ signaling.
Powis
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Arizona Cancer Center, Arizona Health Sciences Center, Tucson 85724.
Seewald
M J
MJ
Melder
D
D
Hoke
M
M
Gratas
C
C
Christensen
T A
TA
Chapman
D E
DE
D016475:3T3 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013498:Suramin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001391:Azo Compounds; D010982:Platelet-Derived Growth Factor; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D002118:Calcium