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首页> 外文期刊>Journal of Cancer Research and Clinical Oncology >Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells.
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Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells.

机译：腺瘤性息肉病大肠杆菌（APC）蛋白水平降低与神经酰胺诱导的结肠癌细胞凋亡有关。

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PURPOSE. Mutations 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, C(2)-ceramide, on different human colon cancer cell lines with and without wild-type p53 and APC genes. METHODS. We studied the effect of C(2)-ceramide and C(2)-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. RESULTS. Our findings indicate that C(2)-ceramide can induce apoptosis independently of the p53/p21(Waf-1/Cip-1) pathway. In addition, the C(2)-ceramide induction of apoptosis showed a correlation with a reduction in the levels of the APC protein and mRNA. Moreover, the C(2)-ceramide-induced apoptosis was blocked by pre-treatment with ZnCl(2), which stabilizes APC protein levels. CONCLUSIONS. These results suggest that C(2)-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 C(2)-ceramide to induce apoptosis of colon cancer cells.
机译：目的。腺瘤性息肉病大肠杆菌（APC）和p53基因的突变通常在大肠癌中发现。因此，我们通过比较天然化学预防剂C（2）-神经酰胺对具有和不具有野生型p53的不同人结肠癌细胞系的影响，分析了APC和p53在诱导结肠癌细胞凋亡中的相对作用。和APC基因。方法。我们研究了C（2）-神经酰胺和C（2）-二氢神经酰胺对结肠癌细胞系体外增殖和/或凋亡的影响，并确定了p53和APC蛋白在这些过程中的作用。分别通过Western和Northern印迹分析确定在处理和未处理的结肠癌细胞系中的蛋白质和mRNA水平。通过FACS分析和PARP-1切割确定细胞周期和凋亡概况。结果。我们的发现表明，C（2）-神经酰胺可以独立于p53 / p21（Waf-1 / Cip-1）途径诱导凋亡。此外，凋亡的C（2）-神经酰胺诱导显示与APC蛋白和mRNA水平降低相关。此外，C（2）-神经酰胺诱导的细胞凋亡被ZnCl（2）预处理阻止，从而稳定了APC蛋白水平。结论。这些结果表明，C（2）-神经酰胺治疗降低了APC蛋白的水平，并且该蛋白水平的降低在C（2）-神经酰胺诱导结肠癌细胞凋亡的能力中起着关键作用。

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