The suppression of prostate LNCaP cancer cells growth by Selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis

Biomaterials. 2011 Sep;32(27):6515-22. doi: 10.1016/j.biomaterials.2011.05.032. Epub 2011 Jun 2.

Abstract

The trace element Selenium is suggested having cancer prevention activity and used as food supplement. Previous results had shown Selenium nanoparticles are safer compared with other Selenium compounds like selenomethionine, sodium selenite and monomethylated Selenium, however, its anticancer activity and intrinsic mechanisms are still elusive. Here, we prepared Selenium nanoparticles and investigated its inherent anticancer mechanisms. We found Selenium nanoparticles inhibit growth of prostate LNCaP cancer cells partially through caspases mediated apoptosis. Selenium nanoparticles suppress transcriptional activity of androgen receptor via down-regulating its mRNA and protein expression. Moreover, Selenium nanoparticles activate Akt kinase by increasing its phosphorylation, promote Akt-dependent androgen receptor phosphorylation and Mdm2 regulated degradation through proteasome pathway. We suggest Selenium nanoparticles suppress prostate cancer cells growth by disrupting androgen receptor, implicating a potential application in cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Light
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Phosphorylation / drug effects
  • Photoelectron Spectroscopy
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Protein Biosynthesis / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Scattering, Radiation
  • Selenium / pharmacology*
  • Transcription, Genetic / drug effects
  • Ubiquitination / drug effects

Substances

  • AR protein, human
  • Receptors, Androgen
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt
  • Caspases
  • Selenium