Cell death induced by
menadione (vitamin K-3,2-methyl-1,4-naphthoquinone) has been investigated in human promyelocytic
leukemia HL-60 cells.
Menadione was found to induce both apoptosis and
necrosis in HL-60 cells. Low concentration (1~50 µM) of
menadione induced apoptotic cell death, which was demonstrated by typical
DNA ladder patterns on
agarose gel electrophoresis and flow cytometry analysis. In contrast, a high concentration of
menadione (100 µM) induced necrotic cell death, which was demonstrated by
DNA smear pattern in
agarose gel electrophoresis. Necrotic cell death was accompanied with a great reduction of cell viability.
Menadione activated
caspase-3, as evidenced by both increased
protease activity and proteolytic cleavage of 116 kDa
poly(ADP-ribose) polymerase (PARP) into 85 kDa cleavage product.
Caspase-3 activity was maximum at 50 µM of
menadione, and very low at 100 µM of
menadione. Taken together, our results showed that menadi-one induced mixed types of cell death, apoptosis at low concentrations and
necrosis at high concentrations in HL-60 cells.