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 α (TNF-α) 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 sevenfold by doxorubicin for the LNCaP line. Both the suramin-TNF-α and the doxorubicin-TNF-α 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-α are active agents against prostate cancer cell lines and that their activity can be enhanced when they are used in combination. [J Natl Cancer Inst 82: 1206-1209, 1990]. © 1990 Oxford University Press.