Synergistic Activity of Suramin With Tumor Necrosis Factor 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.