Suramin interference with transforming growth factor-beta inhibition of human renal cell carcinoma in culture.
Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.
Wade
T P
TP
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kasid
A
A
Stein
C A
CA
LaRocca
R V
RV
Sargent
E R
ER
Gomella
L G
LG
Myers
C E
CE
Linehan
W M
WM
D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D013498:Suramin / Q000037:antagonists & inhibitors*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta; D013498:Suramin