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.
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 kinase 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 MLII-induced apoptosis. Exposure of human leukemia HL-60 cells to various doses of MLII 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 MLII-induced apoptosis. Furthermore, KT5720 and staurospoline, PKA and PKC inhibitors, respectively, reversed the suppression by DB-cAMP and TPA in the MLII-induced apoptosis of HL-60 cells. These results suggest that the activation of PKA or PKC was involved in the suppression of MLII-induced apoptosis in HL-60 cells. Collectively, these results indicate that activation of PKA or PKC in HL-60 cells may confer protection against MLII-induced apoptosis.
Pae
H O
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug, Korea.
Seo
W G
WG
Shin
M
M
Lee
H S
HS
Lee
H S
HS
Kim
S B
SB
Chung
H T
HT
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D003994:Bucladesine / Q000494:pharmacology; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D037102:Lectins / Q000302:isolation & purification / Q000494:pharmacology*; D014784:Mistletoe; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D037102:Lectins; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D011758:Pyrroles; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C057416:KT 5720; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate