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Docosahexaenoic Acid Induces Proteasome‐dependent Degradation of β‐Catenin and Apoptosis in Human Colorectal Cancer Cells not expressing COX‐2
Author(s) -
Calviello Gabriella,
Resci Federica,
Serini Simona,
Piccioni Elisabetta,
Toesca Amelia,
Monego Giovanni,
Ranelletti Franco Oreste,
Palozza Paola
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a30-c
Subject(s) - survivin , apoptosis , catenin , colorectal cancer , cancer research , docosahexaenoic acid , blot , chemistry , cancer cell , biology , polyunsaturated fatty acid , microbiology and biotechnology , cancer , wnt signaling pathway , signal transduction , biochemistry , fatty acid , gene , genetics
Plenty of data show the growth‐inhibitory effects of n‐3 polyunsaturated fatty acids (PUFAs) on colonic cancer cells. Recently, we reported the antiangiogenic and proapoptotic effects of docosahesaenoic acid (DHA) in human cultured colon cancer cells injected in nude mice. The aim of this study was to analyze whether DHA may induce apoptosis in colon cancer cells modifying the expression of β‐catenin. β‐Catenin expression was evaluated by relative quantitative RT‐PCR and Western Blotting. Nuclear β‐catenin was evaluated by indirect immunofluorescence. Apoptosis was evaluated analyzing cells both morphologically and citofluorimetrically (Annexin V‐FITC method). DHA induced a dose‐ and time‐dependent inhibition of β‐catenin protein expression in the cells. The reduction of β‐catenin involved proteasomal degradation accompanied by its reduced translocation into the nucleus, where it acts as a transcription factor. DHA was also able to induce apoptosis and to inhibit the expression of several tumor growth‐related proteins regulated by TCF/β‐catenin pathway (survivin, MT1‐MMP, MMP‐7, and VEGF). We suggest that DHA may exert propoptotic effects through proteasomal regulation of β‐catenin and TCF target gene expression substantiating the hypothesis that DHA may act as a chemopreventive or chemotherapeutic agent against colon cancer. Supported by Italian MUR Grant.