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dc.contributor.authorHu, Ying
dc.contributor.authorMcIntosh, Graeme H
dc.contributor.authorLe Leu, Richard Kevin
dc.contributor.authorNyskohus, Laura S
dc.contributor.authorWoodman, Richard John
dc.contributor.authorYoung, Graeme Paul
dc.date.accessioned2013-04-15T01:28:36Z
dc.date.available2013-04-15T01:28:36Z
dc.date.issued2013-05-23
dc.date.issued2013-05-23
dc.identifier.citationHu, Y., McIntosh, G.H., Le Leu, R.K., Nyskohus, L.S., Woodman, R.J. and Young, G.P., 2013. Combination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkers. PLoS One, 8(5), e64362.en
dc.identifier.urihttp://hdl.handle.net/2328/26688
dc.description.abstractDietary 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, 1ppm selenium as selenium-enriched milk protein, or combination of 1ppm 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.en
dc.language.isoen
dc.publisherPublic Library of Scienceen
dc.relationhttp://purl.org/au-research/grants/nhmrc/1007501en
dc.subjectMedicineen
dc.subjectCancer treatmenten
dc.titleCombination of selenium and green tea improves the efficacy of chemoprevention in a rat colorectal cancer model by modulating genetic and epigenetic biomarkersen
dc.typeArticleen
dc.relation.grantnumberNHMRC/1007501en
dc.rights.licenseCC-BY
local.contributor.authorOrcidLookupLe Leu, Richard Kevin: https://orcid.org/0000-0003-4704-4943en_US


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