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.
Berggren
Margareta
M
Department of Nutritional Sciences, College of Agriculture and Life Sciences, The University of Arizona, Tucson, Arizona 85721-0038, USA.
Sittadjody
Sivanandane
S
Song
Zuohe
Z
Samira
Jean-Louis
JL
Burd
Randy
R
Meuillet
Emmanuelle J
EJ
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