Apoptosis induced by 1 '-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation
J. Moffatt et al., Apoptosis induced by 1 '-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation, CARCINOGENE, 21(12), 2000, pp. 2151-2157
The efficacy of the antitumor activity of 1'-acetoxychavicol acetate (ACA),
reported to be a suppressor of chemically induced carcinogenesis, was eval
uated in Ehrlich ascites tumor cells. ACA treatment resulted in changes in
morphology and a dose-dependent suppression of cell viability. Apoptosis, c
haracterized by nuclear condensation, membrane blebbing, cell shrinkage and
a significant induction of caspase-3-like protease activity at 8 h in a ti
me-course study were observed. Formation of apoptotic bodies was preceded b
y lowering of intracellular polyamines, particularly putrescine, and both d
ose- and time-dependent inhibitory and activation effect by ACA on ornithin
e decarboxylase (ODC) and spermidine/spermine N-1-acetyltransferase (SSAT),
respectively. Administration of exogenous polyamines prevented ACA-induced
apoptosis represented by a reduction in the number of apoptotic bodies and
also caused reduction in the induced caspase-3-like protease activity at 8
h. These findings suggest that the anticarcinogenic effects of ACA might b
e partly due to perturbation of the polyamine metabolic pathway and trigger
ing of caspase-3-like activity, which result in apoptosis.