Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer

  • Authors:
    • Sivalokanathan Sarveswaran
    • Joshua Liroff
    • Zongxiang Zhou
    • Alexander Y. Nikitin
    • Jagadananda Ghosh
  • View Affiliations

  • Published online on: June 1, 2010     https://doi.org/10.3892/ijo_00000627
  • Pages: 1419-1428
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Abstract

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.

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June 2010
Volume 36 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sarveswaran S, Liroff J, Zhou Z, Nikitin AY and Ghosh J: Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer. Int J Oncol 36: 1419-1428, 2010
APA
Sarveswaran, S., Liroff, J., Zhou, Z., Nikitin, A.Y., & Ghosh, J. (2010). Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer. International Journal of Oncology, 36, 1419-1428. https://doi.org/10.3892/ijo_00000627
MLA
Sarveswaran, S., Liroff, J., Zhou, Z., Nikitin, A. Y., Ghosh, J."Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer". International Journal of Oncology 36.6 (2010): 1419-1428.
Chicago
Sarveswaran, S., Liroff, J., Zhou, Z., Nikitin, A. Y., Ghosh, J."Selenite triggers rapid transcriptional activation of p53, and p53-mediated apoptosis in prostate cancer cells: Implication for the treatment of early-stage prostate cancer". International Journal of Oncology 36, no. 6 (2010): 1419-1428. https://doi.org/10.3892/ijo_00000627