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.
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 PPARalpha 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.
Dihal
Ashwin A
AA
TNO Quality of Life, Business Unit Biosciences, Postpunt 8, Zeist, The Netherlands.
van der Woude
Hester
H
Hendriksen
Peter J M
PJ
Charif
Halima
H
Dekker
Lennard J
LJ
Ijsselstijn
Linda
L
de Boer
Vincent C J
VC
Alink
Gerrit M
GM
Burgers
Peter C
PC
Rietjens
Ivonne M C M
IM
Woutersen
Ruud A
RA
Stierum
Rob H
RH
D000818:Animals; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D004032:Diet; D015536:Down-Regulation / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D011794:Quercetin / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344
D005227:Fatty Acids; D020543:Proteome; D011794:Quercetin