Synergistic activity of suramin with tumor necrosis factor alpha and doxorubicin on human prostate cancer cell lines.
We evaluated the action of suramin, doxorubicin, and tumor necrosis factor alpha (TNF-alpha) on the testosterone-responsive human prostate cell line LNCaP and on the testosterone-independent human prostate cell line PC-3. The synergistic action of these agents in combination was tested by the Chou and Talalay method (quantitative analysis of dose-effect relationships) to determine whether in vitro doses were active at levels safely achieved in vivo. The action of suramin was potentiated threefold by doxorubicin for the PC-3 line and seven-fold by doxorubicin for the LNCaP line. Both the suramin-TNF-alpha and the doxorubicin-TNF-alpha combinations showed synergistic action against the LNCaP line. Synergistic activity was noted at drug concentrations routinely achieved clinically. This study demonstrates that suramin, doxorubicin, and TNF-alpha are active agents against prostate cancer cell lines and that their activity can be enhanced when they are used in combination.
Fruehauf
J P
JP
Biochemical Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Myers
C E
CE
Sinha
B K
BK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013498:Suramin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D014409:Tumor Necrosis Factor-alpha; D013498:Suramin; D004317:Doxorubicin