Lack of effect of corticosteroids and tamoxifen on suramin protein binding and in vitro activity.
Stout and colleagues [Proc Am Assoc Cancer Res 1993, 34, p. 298] previously reported that both hydrocortisone and tamoxifen increased the free fraction of suramin in human plasma. We examined several corticosteroids as well as tamoxifen for their effects on suramin protein binding and also evaluated hydrocortisone for its ability to modulate suramin activity in PC-3 and MCF-7 cells. Greater than 99% of the suramin was protein bound in undiluted human plasma. However, the free fraction of suramin was increased with the reduced plasma protein levels and increased suramin concentrations. At concentrations ranging from 1 to 30 microM, neither tamoxifen, hydrocortisone, prednisone nor dexamethasone had any effect on the binding of suramin to human plasma, regardless of protein concentrations. Similar results were observed with fetal calf serum. Hydrocortisone also had no effect on suramin activity against PC-3 and MCF-7 cell in vitro. We conclude from these studies that neither corticosteroids nor tamoxifen affect suramin protein binding or its cytotoxic activity.
Driscoll
D L
DL
Department of Cancer Research, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.
Steinkampf
R W
RW
Paradiso
L J
LJ
Kowal
C D
CD
Klohs
W D
WD
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D013498:Suramin / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D001798:Blood Proteins; D005938:Glucocorticoids; D013629:Tamoxifen; D013498:Suramin; D006854:Hydrocortisone