CANCER CELL SENSITIZATION TO FAS-MEDIATED APOPTOSIS BY SODIUM-BUTYRATE

Cancer cells often resist Fas-mediated apoptosis even when the Fas rec eptor is expressed at the cell surf ace. We show here that human and r at colon cancer cells undergo massive apoptosis when they are exposed to soluble Fas ligand in the presence of sodium butyrate, an agent tha t induces by itself only a low rate of apoptosis, Sodium butyrate pote ntiates Fas-dependent apoptosis in seven out of eight colon cancer cel l lines, Sodium butyrate does not increase Fas receptor cell surface e xpression and does not modify cell levels of Bcl-2, Bcl-x(L), Bcl-x(S) and Bar. Sodium butyrate also induces tumor cell sensitization to the apoptotic effect of the combination of TNF-alpha and IFN-gamma, but i t does not modify the level of the FADD/Mort1 adaptator molecule, at t he connection between Fas- and TNF-dependent apoptosis pathways. Becau se the clinical toxicity of butyrate is low, its ability to enhance Fa s-signal delivery in cancer cells could be of therapeutic interest.