Apoptosis induced by 1 '-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation

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.