Camptothecin sensitizes androgen-independent prostate cancer cells to antiFas-induced apoptosis

Despite expressing both Fas and Fas ligand, DU145 and LNCaP prostate cancer cells were resistant to anti-fas-induced cell death. Resistance to Fas-med iated cytotoxicity could be overcome in DU145, but not in LNCaP, cells by p retreating cells with sublethal doses of cytotoxic drugs, such as camptothe cin. Activated caspases were shown to be required for this cytotoxicity. In deed, poly(ADP-Ribose) polymerase was shown to be proteolytically cleaved i n cells treated with camptothecin plus anti-fas, but not in cells treated w ith anti-fas only. Moreover, pretreatment of cells with ZVAD completely blo cked camptothecin-mediated Fas-induced apoptosis. Sensitization of cells to Fas-induced cell death did not involve up-regulation of Fas or Fast, and i t was independent of alterations in the cell cycle. Reactive oxygen interme diates (ROI) have been shown to be important mediators of drug-induced apop tosis. Here, we demonstrate that treatment of DU145 cells with camptothecin , anti-fas, or both, did not alter the intracellular levels of peroxide or superoxide anion.