Molecular chemoprevention by selenium: A genomic approach

El‐Bayoumy, Karam; Sinha, Raghu

doi:10.1016/j.mrfmmm.2005.04.021

Cited by 123 publications

(175 citation statements)

References 62 publications

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“…Such induction of DNA synthesis without subsequent cell division should result in appearance of polyploid hepatocytes, a potential source of chromosomal aberrations. In the majority of tested animal and cell culture cancer models, selenium compounds decreased expression of several cell cycle genes, including PCNA and cyclin D1 (21). In Mdr2-KO mice, selenomethionine inhibited PCNA expression both at the mRNA and protein levels; inhibitory effect of tannic acid on PCNA expression was less pronounced (Fig.…”

Section: Discussionmentioning

confidence: 95%

“…In animal cancer models, selenomethionine and selenocysteine are the most efficient chemopreventive selenium compounds (19). In addition to its role as an essential component of two antioxidant enzymes (thioredoxin reductase and glutathione peroxidase), selenium affects many cellular regulatory pathways (20,21). Thus, for both tannic acid and selenomethionine, their chemopreventive activity on hepatocellular carcinoma could be attributed not only to an increase in antioxidant protection systems in the liver but also to their effects on the immune system, angiogenesis, and cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice

Katzenellenbogen¹,

Mizrahi²,

Pappo

et al. 2007

Molecular Cancer Therapeutics

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Dietary antioxidants and selenium compounds were shown to have a therapeutic effect against hepatocellular carcinoma in several mouse models. We tested the effects of tannic acid and selenomethionine on hepatocellular carcinoma development in Mdr2 knockout (Mdr2-KO) mice. Mdr2-KO and age-matched Mdr2 heterozygous control mice were fed with tannic acid or selenomethionine during the first 3 months of life. Then, several mice from each group were sacrificed, and liver tissue samples were removed for analysis. The remaining mice were fed a regular diet until the age of 16 months, at which time the number and size of liver tumors were determined. Liver tissue samples of 3-month-old mice were subjected to gene expression profiling analysis using cDNA macroarrays containing probes for 240 genes that regulate responses to oxidative stress and inflammation or lipid metabolism. Both tannic acid and selenomethionine had partial chemopreventive effect on development of hepatocellular carcinoma in Mdr2-KO mice: they reduced the incidence of large tumor nodules (diameter >1 cm) at age 16 months. Both agents inhibited gene expression and reversed up-regulation of many genes that control inflammation or response to oxidative stress in Mdr2-KO livers at age 3 months. This inhibitory effect on gene expression correlated with the ability of agents to reduce incidence of large tumors: selenomethionine was more active than tannic acid in both aspects. Understanding the molecular mechanism of chemoprevention effect could improve our therapeutic modalities while using these agents. [Mol Cancer Ther 2007;6(4):1283 -91]

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice

Katzenellenbogen¹,

Mizrahi²,

Pappo

et al. 2007

Molecular Cancer Therapeutics

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“…Thus, the selenium content differed by a factor of 100, whereas in the present study the factor was only 2. The conflicting results (reviewed in [13]) can be explained by the fact that a supranutritional diet can induce phase II enzymes much more efficiently than selenium-deficiency can do. Taking the supranutritional diet as reference for the and duodenum (n = 6) of selenium-poor (-Se) relative to seleniumadequate (?Se) mice.…”

Section: Discussionmentioning

confidence: 99%

“…However, several microarray studies revealed that the expression of also non-selenoproteins is influenced by the availability of selenium (reviewed in [13]). Underlying mechanisms are still scarce.…”

Section: Introductionmentioning

confidence: 99%

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Nrf2 target genes are induced under marginal selenium-deficiency

et al. 2010

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A suboptimal selenium supply appears to prevail in Europe. The current study, therefore, was focused on the changes in gene expression under a suboptimal selenium intake. Previous microarray analyses in the colon of mice fed either a selenium-adequate or a moderately deficient diet revealed a change in genes of several pathways. Severe selenium-deficiency has been found previously to influence Nrf2-regulated genes of the adaptive response. Since the previous pathway analyses were done with a program not searching for Nrf2 target genes, respective genes were manually selected and confirmed by qPCR. qPCR revealed an induction of phase II (Nqo1, Gsts, Sult1b1 and Ugt1a6) and antioxidant enzymes (Hmox1, Mt2, Prdx1, Srxn1, Sod1 and Gclc) under the selenium-poor diet, which is considered to compensate for the loss of selenoproteins. The strongest effects were observed in the duodenum where preferentially genes for antioxidant enzymes were up-regulated. These also include the mRNA of the selenoproteins TrxR1 and GPx2 that would enable their immediate translation upon selenium refeeding. The down-regulation of Gsk3b in moderate selenium-deficiency observed in the previous paper provides a possible explanation for the activation of the Nrf2 pathway, because inhibition of GSK3b results in the nuclear accumulation of Nrf2.

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