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Journal of Cancer Research and Clinical Oncology

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01.12.2004 | Original Paper

Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells

verfasst von: Aruna S. Jaiswal, Satya Narayan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2004

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Abstract

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, C₂-ceramide, on different human colon cancer cell lines with and without wild-type p53 and APC genes.

Methods

We 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.

Results

Our 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.

Conclusions

These 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.

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Titel: Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells
verfasst von: Aruna S. Jaiswal
Satya Narayan
Publikationsdatum: 01.12.2004
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2004
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-004-0591-6

Springer Medizin

Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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