Protein Kinase a or C Modulates the Apoptosis Induced by Lectin II Isolated from Korean Mistletoe, Viscum Album Var. Coloratum, in the Human Leukemic HL-60 Cells

Abstract

Mistletoe lectins (MLs) are increasingly used as an anticancer drug in the treatment of human tumors. The cytotoxic activity of MLs against tumor cells is due to programmed cell death (apoptosis). The up-or down-regulation of protein kinas A (PKA) or C (PKC) is known to be associated with the regulation of drug-induced apoptosis. Previously, we isolated cytotoxic MLII from the extract of Korean mistletoe (Viscum album var. Coloratum) and characterized its biochemical properties. The present study was designed to investigate the role of PKA and PKC in ML II-induced apoptosis. Exposure of human leukemia HL-60 cells to various doses of ML II resulted in apoptosis. However, the treatment of these cells with dibutyl-cyclic AMP (DB-cAMP), PKA activator, or 12-O-tertadecanoyl phorbol 13-acetate (TPA), PKC activator, suppressed ML II-induced apoptosis. Furthermore, KT5720 and staurospoline, PKA and PKC inhibitors, respectively, reversed the suppression by DB-cAMP and TPA in the ML II-induced apoptosis of HL-60 cells. These results