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 evaluated in Ehrlich ascites tumor cells. ACA treatment resulted in changes in morphology and a dose-dependent suppression of cell viability. Apoptosis, characterized by nuclear condensation, membrane blebbing, cell shrinkage and a significant induction of caspase-3-like protease activity at 8 h in a time-course study were observed. Formation of apoptotic bodies was preceded by lowering of intracellular polyamines, particularly putrescine, and both dose- and time-dependent inhibitory and activation effect by ACA on ornithine 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 be partly due to perturbation of the polyamine metabolic pathway and triggering of caspase-3-like activity, which result in apoptosis.
Moffatt
J
J
Department of Food and Nutrition, Faculty of Human Life Science, Osaka, City University, Osaka 558-8585, Japan.
Hashimoto
M
M
Kojima
A
A
Kennedy
D O
DO
Murakami
A
A
Koshimizu
K
K
Ohigashi
H
H
Matsui-Yuasa
I
I
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001592:Benzyl Alcohols; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D007700:Kinetics; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D013729:Terpenes / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D016588:Anticarcinogenic Agents; D001592:Benzyl Alcohols; D053148:Caspase 3; D020169:Caspases; D009955:Ornithine Decarboxylase; D011073:Polyamines; D013729:Terpenes; D000099228:Diamine N-Acetyltransferase; C505409:Casp3 protein, mouse; C047948:1'-acetoxychavicol acetate