Journal Article

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

Jerry Moffatt, Makiko Hashimoto, Akiko Kojima, David Opare Kennedy, Akira Murakami, Koichi Koshimizu, Hajime Ohigashi and Isao Matsui-Yuasa

in Carcinogenesis

Volume 21, issue 12, pages 2151-2157
Published in print December 2000 | ISSN: 0143-3334
Published online December 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.12.2151
Apoptosis induced by 1′-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation

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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 N1-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.

Keywords: ACA, 1′-acetoxychavicol acetate; AP-1, activated protein 1; DAPI, 4′,6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide; DTT, dithiothreitol; FCS, fetal calf serum; ICE, interleukin-1β-converting enzyme; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; NMBA, N-nitrosomethylbenzylamine; ODC, ornithine decarboxylase; PBS, phosphate-buffered saline; ROS, reactive oxygen species; SSAT, spermidine/spermine N1-acetyltransferase; TPA, 12-O-tetradecanoylphorbol-13-acetate.

Journal Article.  5412 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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