Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells.
Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells.
复制标题
腺瘤性结肠息肉病 (APC) 蛋白水平降低与神经酰胺诱导的结肠癌细胞凋亡有关。
DOI：
10.1007/s00432-004-0591-6
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发表时间：
2004
影响因子：
3.6
通讯作者：
Narayan,Satya
中科院分区：
文献类型：
--
作者：
Jaiswal,ArunaS;Narayan,Satya
目的大肠腺瘤性息肉病（APC）和p53基因突变在大肠癌中普遍存在。因此，我们通过比较天然化学预防剂C2-神经酰胺，方法我们研究了C2-神经酰胺和C2-二氢神经酰胺对不同的人结肠癌细胞系（有和没有野生型p53和APC基因）增殖和/或凋亡的影响。或体外结肠癌细胞系的凋亡，并确定p53和APC蛋白在这些过程中的作用。分别通过蛋白质印迹和北方印迹分析来测定经处理和未经处理的结肠癌细胞系中的蛋白质和mRNA水平。流式细胞仪分析和PARP-1 cleaving.ResultsC2-ceramide的细胞周期和细胞凋亡的配置文件进行了测定，我们的研究结果表明，C2-神经酰胺可以诱导凋亡的p53/p21（Waf-1/Cip-1）通路独立。此外，C2-神经酰胺诱导的细胞凋亡与APC蛋白和mRNA水平的降低相关。此外，C2-神经酰胺诱导的细胞凋亡被阻断预处理与ZnCl 2，这稳定APC蛋白levels.ConclusionsThese结果表明，C2-神经酰胺治疗降低APC蛋白的水平，这种蛋白质的水平的减少起着关键作用的C2-神经酰胺诱导结肠癌细胞凋亡的能力。
PurposeMutations of the adenomatous polyposis coli (APC) and p53 genes are commonly found in colorectal cancers. We therefore analyzed the relative roles of APC and p53 in the induction of apoptosis of colon cancer cells by comparing the effects of the natural chemopreventive agent, C2-ceramide, on different human colon cancer cell lines with and without wild-type p53 and APC genes.MethodsWe studied the effect of C2-ceramide and C2-dihydroceramide on proliferation and/or apoptosis of colon cancer cell lines in vitro and determined the role of p53 and APC proteins in these processes. The protein and mRNA levels in colon cancer cell lines with and without treatments were determined by Western and Northern blot analysis, respectively. The cell cycle and apoptosis profiles were determined by FACS analysis and PARP-1 cleavage.ResultsOur findings indicate that C2-ceramide can induce apoptosis independently of the p53/p21(Waf-1/Cip-1) pathway. In addition, the C2-ceramide induction of apoptosis showed a correlation with a reduction in the levels of the APC protein and mRNA. Moreover, the C2-ceramide-induced apoptosis was blocked by pre-treatment with ZnCl2, which stabilizes APC protein levels.ConclusionsThese results suggest that C2-ceramide treatment reduces the levels of APC protein and that the reduction in the levels of this protein plays a key role in the ability of C2-ceramide to induce apoptosis of colon cancer cells.