Selenoprotein deficiency and high levels of selenium compounds can effectively inhibit hepatocarcinogenesis in transgenic mice.
The micronutrient element selenium (Se) has been shown to be effective in reducing the incidence of cancer in animal models and human clinical trials. Selenoproteins and low molecular weight Se compounds were implicated in the chemopreventive effect, but specific mechanisms are not clear. We examined the role of Se and selenoproteins in liver tumor formation in TGFalpha/c-Myc transgenic mice, which are characterized by disrupted redox homeostasis and develop liver cancer by 6 months of age. In these mice, both Se deficiency and high levels of Se compounds suppressed hepatocarcinogenesis. In addition, both treatments induced expression of detoxification genes, increased apoptosis and inhibited cell proliferation. Within low-to-optimal levels of dietary Se, tumor formation correlated with expression of most selenoproteins. These data suggest that changes in selenoprotein expression may either suppress or promote tumorigenesis depending on cell type and genotype. Since dietary Se may have opposing effects on cancer, it is important to identify the subjects who will benefit from Se supplementation as well as those who will not.
Novoselov
Sergey V
SV
Department of Biochemistry, University of Nebraska, N 151 Beadle Center, 1901 Vine Street, Lincoln, NE 68588, USA.
Calvisi
Diego F
DF
Labunskyy
Vyacheslav M
VM
Factor
Valentina M
VM
Carlson
Bradley A
BA
Fomenko
Dmitri E
DE
Moustafa
Mohamed E
ME
Hatfield
Dolph L
DL
Gladyshev
Vadim N
VN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000187:drug effects; D018036:Selenium Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D012644:Selenium Radioisotopes; D051140:Selenoproteins / Q000172:deficiency*; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D018036:Selenium Compounds; D012644:Selenium Radioisotopes; D051140:Selenoproteins; D005979:Glutathione Peroxidase; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase; C516125:Txnrd1 protein, mouse; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse