We studied the effect of momordin I, a compound purified from a plant, Ampelopsis japonica, on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Momordin I was cytotoxic to HL-60 cells with an IC50 of 19.0 microg/ml. The antiproliferative effects of momordin I appear to be attributable to its induction of apoptotic cell death, as momordin I induced nuclear morphology changes and internucleosomal DNA fragmentation and it increased the proportion of hypodiploid cells. Momordin I treatment also gradually decreased the expression of.the anti-apoptotic protein Bcl-2, but increased the expression of the pro-apoptotic protein Bax. In addition, momordin I treatment increased the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase. In this study we showed that momordin I induced apoptosis of HL-60 cells by reduction of the Bcl-2:Bax ratio and by activation of caspase-3. These results provide important information towards understanding the mechanism by which momordin I induces apoptosis.