Protein kinase A or C modulates the apoptosis induced by lectin II isolated from Korean mistletoe, Viscum album var. Coloratum, in the human leukemicHL-60 cells

Mistletoe lectins (MLs) are increasingly used as an anticancer drug in the treatment of human tumors. The cytotoxic activity of MLs against tumor cell s is due to programmed cell death (apoptosis). The up- or down-regulation o f protein kinas A (PKA) or C (PKC) is known to be associated with the regul ation of drug-induced apoptosis. Previously, we isolated cytotoxic ML II fr om the extract of Korean mistletoe (Viscum album var. Coloratum) and charac terized its biochemical properties. The present study was designed to inves tigate the role of PKA and PKC in ML II-induced apoptosis. Exposure of huma n leukemia HL-60 cells to various doses of ML II resulted in apoptosis. How ever, the treatment of these cells with dibutyl-cyclic AMP (DB-cAMP), PKA a ctivator, or 12-O-tertadecanoyl phorbol 13-acetate (TPA), PKC activator, su ppressed ML II-induced apoptosis. Furthermore, KT5720 and staurospoline, PK A and PKC inhibitors, respectively, reversed the suppression by DB-cAMP and TPA in the ML II-induced apoptosis of HL-60 cells. These results suggest t hat the activation of PKA or PKC was involved in the suppression of ML II-i nduced apoptosis in HL-60 cells. Collectively, these results indicate that activation of PKA or PKC in HL-60 cells may confer protection against ML II -induced apoptosis.