Activation of caspase cascades in Korean mistletoe (Viscum album var. coloratum) lectin-II-induced apoptosis of human myeloleukemic U937 cells

Mistletoe lectins are of high biological activity and exert cytotoxic effec ts. We have previously shown that Korean mistletoe, Viscum album var. color artum, lectin-II specifically induces apoptotic cell death in cancer cells, not normal lymphocytes. The destructive mechanism by mistletoe lectins on tumor cells was mediated by activation of c-JUN N-terminal kinase (JNK)/str ess-activated protein kinase. Herein, we investigated the involvement of ca spase cascade and its proteolytic cleavage effects on biosubstrates of huma n myeloleukemic U937 cells by D-galactoside and N-acetyl-galactosamine-spec ific Korean mistletoe lectin-II. Mistletoe lectin-II induced ladder pattern DNA fragmentation and activation of caspase-3, -8, and -9 of U937 cells, b ut not caspase-1 protease, in a time- and dose-dependent manner. Consistent with catalytic activation of protease, both poly(ADP-ribose) polymerase (P ARP) and protein kinase C-delta (PKC-delta) are also cleaved in mistletoe l ectin-II-treated U937 cells. An inhibitor of caspase-3-like protease, DEVD- CHO peptide, significantly inhibited mistletoe lectin-II-induced apoptosis, PARP cleavage, and fragmentation of DNA. These results provide the evidenc e that Korean mistletoe lectin-II induces apoptotic death of U937 cells via activation of caspase cascades. (C) 2001 Elsevier Science Inc. All rights reserved.