Sodium selenite increases the activity of the tumor suppressor protein, PTEN, in DU-145 prostate cancer cells.
Epidemiological and clinical data suggest that selenium may prevent prostate cancer; however, the cellular effects of selenium in malignant prostate cells are not well understood. We previously reported that the activity of the tumor suppressor PTEN is modulated by thioredoxin (Trx) in a RedOx-dependent manner. In this study, we demonstrated that the activity of Trx reductase (TR) is increased by sevenfold in the human prostate cancer cell line, DU-145, after 5 days of sodium selenite (Se) treatment. The treatment of DU-145 cells with increasing concentrations of Se induced an increase in PTEN lipid phosphatase activity by twofold, which correlated with a decrease in phospho-ser(473)-Akt, and an increase in phospho-Ser(370)-PTEN levels. Se also increased casein kinase-2 (CK2) activity; and the use of apigenin, an inhibitor of CK2, revealed that the regulation of the tumor suppressor PTEN by Se may be achieved via both the Trx-TR system and the RedOx control of the kinase involved in the regulation of PTEN activity.
Department of Nutritional Sciences, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona 85721-0038, USA.
Margareta
M
Berggren
Sivanandane
S
Sittadjody
Zuohe
Z
Song
Jean-Louis
JL
Samira
Randy
R
Burd
Emmanuelle J
EJ
Meuillet
D047390:Casein Kinase II / Q000502:physiology; D045744:Cell Line, Tumor; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D025521:Tumor Suppressor Proteins; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005978:Glutathione; D018038:Sodium Selenite