N. Sata et al., MENADIONE INDUCES BOTH NECROSIS AND APOPTOSIS IN RAT PANCREATIC ACINAR AR4-2J CELLS, Free radical biology & medicine, 23(6), 1997, pp. 844-850
This study evaluated the action of menadione on cell proliferation and
integrity of the rot pancreatic acinar cell line, AR4-2J. Menadione a
t 1-20 mu M dose-and time-dependently inhibited cell proliferation of
AR4-2J cells. In contrast, a high concentration of menadione (100 mu M
) caused rapid cell death (> 90% of cells took up trypan blue within 4
-h). While the high concentration of menadione (100 mu M) induced DNA
smear in electrophoresis indicative of necrosis, lower concentrations
(10-20 mu M) induced a DNA ladder indicative of apoptosis, Similar res
ults were obtained using a DNA fragmentation ELISA. Glutathione (1 mM)
, the calcium chelator EGTA (500 mu M), and the cystein protease inhib
itor NCO-700 (5 mM) partly inhibited the effect of 1-10 mu M menadione
on cell proliferation and DNA fragmentation. Menadione at 1-20 mu M i
nduced wild-type P53, whereas the 100 mu M menadione had a minor effec
t on wild-type P53. It is concluded that menadione induced necrosis at
high concentrations and apoptosis at low concentrations in AR4-2J cel
ls. Apoptosis induced by lower concentrations of menadione may be medi
ated by wild-type P53, intracellular calcium, and mechanisms which dec
rease the intracellular concentration of reduced glutathione. (C) 1997
Elsevier Science Inc.