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Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis

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Author: Dihal, A.A. · Woude, H. van der · Hendriksen, P.J.M. · Charif, H. · Dekker, L.J. · IJsselstijn, L. · Boer, V.C.J. de · Alink, G.M. · Burgers, P.C. · Rietjens, I.M.C.M. · Woutersen, R.A. · Stierum, R.H.
Institution: TNO Kwaliteit van Leven · KvL
Source:Proteomics, 1, 8, 45-61
Identifier: 240575
doi: doi:10.1002/pmic.200700364
Keywords: Biology · Toxicology and Applied Pharmacology · Biomarker · Colorectal cancer · Quercetin · Transcriptomics · fatty acid · glutathione peroxidase 2 · heat shock protein · mitogen activated protein kinase · peroxisome proliferator activated receptor alpha · quercetin · transcriptome · animal experiment · animal model · article · cancer prevention · cell cycle · colon mucosa · colorectal cancer · controlled study · down regulation · energy metabolism · Fischer 344 rat · gene expression · gene targeting · genetic analysis · glycolysis · lipid degradation · male · nonhuman · nucleotide sequence · priority journal · proteomics · rat · statistical significance · tumor biopsy · Animals · Colon · Colorectal Neoplasms · Diet · Down-Regulation · Fatty Acids · Gene Expression Profiling · Glycolysis · Intestinal Mucosa · Male · Mitochondria · Proteome · Quercetin · Rats · Rats, Inbred F344 · Rattus


Quercetin has been shown to act as an anticarcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterize transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 wk. Transcriptome data analyzed with Gene Set Enrichment Analysis showed that quercetin significantly downregulated the potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In addition, quercetin enhanced expression of tumor suppressor genes, including Pten, Tp53, and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore, dietary quercetin enhanced genes involved in phase I and II metabolism, including Fmo5, Ephx1, Ephx2, and Gpx2. Quercetin increased PPARα target genes, and concomitantly enhanced expression of genes involved in mitochondrial fatty acid (FA) degradation. Proteomics performed in the same samples revealed 33 affected proteins, of which four glycolysis enzymes and three heat shock proteins were decreased. A proteome-transcriptome comparison showed a low correlation, but both pointed out toward altered energy metabolism. In conclusion, transcriptomics combined with proteomics showed that dietary quercetin evoked changes contrary to those found in colorectal carcinogenesis. These tumor-protective mechanisms were associated with a shift in energy production pathways, pointing at decreased cytoplasmic glycolysis and toward increased mitochondrial FA degradation. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA. Molecular Sequence Numbers: GENBANK: A23126, A24639, A26186, A26468, A35340, A35865, A40452, A54889, AAA18026, AAA40933, AAB23369, AAC52676, AAH62238, AAH64440, AAH78829, AAH87023, AAP13984, BAA28215, CAA65655, I52328, I65237, Q63654, S17189; Chemicals / CAS: mitogen activated protein kinase, 142243-02-5; peroxisome proliferator activated receptor alpha, 147258-70-6; quercetin, 117-39-5; Fatty Acids; Proteome; Quercetin, 117-39-5