Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer.
Supra-nutritional selenium supplementation has emerged as an attractive new approach to intervene in a range of human cancers, in particular prostate cancer. However, scanty information is currently available on molecular mechanisms underlying selenium's anticancer action. The tumor suppressor p53 plays an important role in preventing transformation by transcriptional regulation of a range of genes that are involved in vital cell functions such as DNA repair, cell cycle arrest, and induction of apoptosis. Here we report that incubation of LNCaP human prostate cancer cells (p53 +/+) with a natural form of selenium triggers rapid transcriptional activation of p53, and up-regulation of the expression of p53-target genes as well as induction of miR-34 class of microRNAs. Moreover, blocking p53 function by transfection of cells with a dominant-negative, mutated p53 gene, or by siRNA, significantly reduced selenium-induced expression of p53-target genes and induction of apoptosis. Since majority of the early-stage human prostate cancers bear functional p53 gene (p53+/+), our findings indicate that the anticancer action of selenium may involve transactivation of p53 as a potential mechanism, and suggest that selenite may be useful not only for prevention but also for treatment of human prostate cancer.
Sarveswaran
Sivalokanathan
S
The Vattikuti Urology Institute, Department of Urology, Henry Ford Health System, Detroit, MI 48202, USA.
Liroff
Joshua
J
Zhou
Zongxiang
Z
Nikitin
Alexander Y
AY
Ghosh
Jagadananda
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018038:Sodium Selenite / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D018038:Sodium Selenite