RGD Reference Report - Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers. - Rat Genome Database

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Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers.

Authors: Hu, Y  McIntosh, GH  Le Leu, RK  Nyskohus, LS  Woodman, RJ  Young, GP 
Citation: Hu Y, etal., PLoS One. 2013 May 23;8(5):e64362. doi: 10.1371/journal.pone.0064362. Print 2013.
RGD ID: 9588299
Pubmed: PMID:23717604   (View Abstract at PubMed)
PMCID: PMC3662759   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0064362   (Journal Full-text)

Dietary supplementation of selenium and green tea holds promise in cancer prevention. In this study, we evaluated the efficacies of selenium and green tea administered individually and in combination against colorectal cancer in an azoxymethane (AOM)-induced rat colonic carcinogenesis model and determined the underlying mechanisms of the protection. Four-week old Sprague-Dawley male rats were fed with diets containing 0.5% green tea extract, 1 ppm selenium as selenium-enriched milk protein, or combination of 1 ppm selenium and 0.5% green tea extract. Animals received 2 AOM (15 mg/kg) treatments to induce colonic oncogenesis. Rats were killed 8 or 30 wk later after the last AOM to examine the effect of dietary intervention on aberrant crypt foci (ACF) formation or tumor development. On sacrifice, colons were examined for ACF and tumors, the mRNA levels of SFRP5 and Cyclin D1, and the proteins levels of ss-catenin, COX-2, Ki-67, DNMT1 and acetyl histone H3. The combination of selenium and green tea resulted in a significant additive inhibition of large ACF formation, this effect was greater than either selenium or green tea alone, P<0.01; the combination also had a significant additive inhibition effect on all tumor endpoints, the effect of the combination diet on tumor incidence, multiplicity and size was greater than selenium or green tea alone, P<0.01. Rats fed the combination diet showed marked reduction of DNMT1 expression and induction of histone H3 acetylation, which were accompanied by restoration of SFRP5 mRNA in normal-appearing colonic crypts. The combination diet also significantly reduced ss-catenin nuclear translocation, Cyclin D1 expression and cell proliferation. These data show, for the first time, that combination of selenium and green tea is more effective in suppressing colorectal oncogenesis than either agent alone. The preventive effect is associated with regulation of genetic and epigenetic biomarkers implicated in colonic carcinogenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Colorectal Neoplasms treatmentISODnmt1 (Rattus norvegicus)9588299; 9588299 RGD 
Colorectal Neoplasms treatmentIEP 9588299 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dnmt1  (DNA methyltransferase 1)

Genes (Mus musculus)
Dnmt1  (DNA methyltransferase 1)

Genes (Homo sapiens)
DNMT1  (DNA methyltransferase 1)


Additional Information