Apoptosis induced by 1′-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation
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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DOI：
10.1093/carcin/21.12.2151
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发表时间：
2000-12-01
期刊：
影响因子：
4.7
通讯作者：
Matsui-Yuasa, I
中科院分区：
文献类型：
--
作者：
Moffatt, J;Hashimoto, M;Matsui-Yuasa, I
用埃利希腹水癌细胞评价了1 '-乙酰氧基胡椒酚乙酸酯（ACA）的抗肿瘤活性。ACA处理导致形态学的变化和细胞活力的剂量依赖性抑制。细胞凋亡，其特征在于核浓缩，膜起泡，细胞皱缩和一个显着的诱导caspase-3样蛋白酶活性在8小时的时间过程中的研究进行了观察。凋亡小体的形成之前，降低细胞内的多胺，特别是腐胺，和两个剂量和时间依赖性的抑制和激活作用ACA上的鸟氨酸脱羧酶（ODC）和亚精胺/精胺N-1-乙酰转移酶（SSAT），分别。外源性多胺的管理防止ACA诱导的细胞凋亡的凋亡小体的数量减少，并在8小时诱导的半胱天冬酶-3样蛋白酶活性的减少。这些结果表明，ACA的抗癌作用可能部分是由于干扰多胺代谢途径和触发caspase-3样活性，从而导致细胞凋亡。
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.