Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells
Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells
复制标题
DOI：
10.1111/j.1349-7006.2003.tb01358.x
复制
发表时间：
2003-01-01
期刊：
影响因子：
5.7
通讯作者：
Ikejima, T
中科院分区：
文献类型：
--
作者：
Fei, XF;Wang, BX;Ikejima, T
我们发现吴茱萸中的主要生物碱成分吴茱萸碱能抑制多种肿瘤细胞系的增殖，但对人外周血单核细胞(PBMC)的作用较小。我们以人宫颈癌细胞HeLa为模型，阐明吴茱萸碱诱导肿瘤细胞死亡的分子机制。结果表明，吴茱萸碱在体外可引起HeLa细胞DNA寡核体断裂，caspase-3活性升高，但caspase-1活性无明显变化。Caspase-3抑制剂z-DEVD-fmk(z-Asp-Glu-Val-Asp-fmk)能有效抑制吴茱萸碱诱导的DNA断裂和caspase-3活性。此外，吴茱萸碱还能增加线粒体中凋亡诱导因子Bax的表达，降低凋亡抑制因子Bcl2的表达。综上所述，我们的研究结果表明吴茱萸碱改变了HeLa细胞中Bcl2和Bax基因表达的平衡，并通过caspase途径诱导细胞凋亡。
We found that evodiamine, a major alkaloidal component of Evodiae Fructus (Goshuyu in Japan), inhibited proliferation of several tumor cell lines, but had less effect on human peripheral blood mononuclear cells (PBMC). We used human cervical cancer cells, HeLa, as a model to elucidate the molecular mechanisms of evodiamine-induced tumor cell death. The results showed that evodiamine induced oligonucleosomal fragmentation of DNA in HeLa cells and increased the activity of caspase-3, but not that of caspase-1, in vitro. Both evodiamine-induced DNA fragmentation and caspase-3 activity were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). In addition, evodiamine increased the expression of the apoptosis inducer Bax, but decreased the expression of the apoptosis suppressor Bcl-2 in mitochondria. Taken together, our data indicated that evodiamine alters the balance of Bcl-2 and Bax gene expression and induces apoptosis through the caspase pathway in HeLa cells.