HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR ACTIVATES THE APOPTOSIS SIGNALING PATHWAY BY INCREASING CASPASE-3 ACTIVITY IN SARCOMA-180 CELLS

Hepatocyte growth factor, which is now known to be the same protein as scatter factor, induced oligonucleosomal fragmentation of nuclear DNA of Sarcoma 180 cells and increased the activity of caspase-3, a key c omponent in control of the apoptotic cell death pathway to about 2.6 t imes that in control cells on 48 hr incubation, but did not increase t he activity of caspase-1. Both HGF-induced DNA fragmentation and caspa se-3 activity were completely inhibited by co-incubation with an inhib itor of caspase-3, Ac-DEVD-H. In contrast, HGF did not affect the expr ession of the apoptosis suppressors Bcl-2 and Bcl-x, These results ind icate that HGF activates the apoptosis signaling pathway by increasing caspase-3 activity in Sarcoma 180 cells. (C) 1998 Academic Press.