STAT-1-independent upregulation of FADD and procaspase-3 and -8 in cancer cells treated with cytotoxic drugs

We have previously shown that treatment by anticancer drugs sensitized tumo r cells to Fas (APO-1/CD95)-mediated cell death. The present study demonstr ates that the cytotoxic drugs cisplatin, doxorubicin and mitomycin C induce the accumulation of the Fas receptor, the FADD adaptor molecule, the proca spases-8, -3 and -2L and the proapoptotic molecule Bar in several human col on cancer cells. This upregulation is also observed in U3A myeloblastoma ce lls that do not express STAT-1, a transcription factor involved in the cons titutive expression of procaspases. We conclude that anticancer drugs sensi tize tumor cells to Fas-mediated cell death by a STAT-1-independent upregul ation of molecules involved in this apoptotic pathway, (C) 1999 Academic Pr ess.