Silver-based nanoparticles induce apoptosis in human colon cancer cells mediated through p53

Nanomedicine (Lond). 2013 Aug;8(8):1307-22. doi: 10.2217/nnm.12.176. Epub 2013 Mar 21.

Abstract

Aim: The authors have systematically investigated the anticancer potentiality of silver-based nanoparticles (AgNPs) and the mechanism underlying their biological activity in human colon cancer cells.

Materials & methods: Starch-capped AgNPs were synthesized, characterized and their biological activity evaluated through multiple biochemical assays.

Results: AgNPs decreased the growth and viability of HCT116 colon cancer cells. AgNP exposure increased apoptosis, as demonstrated by an increase in 4´,6-diamidino-2-phenylindole-stained apoptotic nuclei, BAX/BCL-XL ratio, cleaved poly(ADP-ribose) polymerase, p53, p21 and caspases 3, 8 and 9, and by a decrease in the levels of AKT and NF-κB. The cell population in the G1 phase decreased, and the S-phase population increased after AgNP treatment. AgNPs caused DNA damage and reduced the interaction between p53 and NF-κB. Interestingly, no significant alteration was noted in the levels of p21, BAX/BCL-XL and NF-κB after AgNP treatment in a p53-knockout HCT116 cell line.

Conclusion: AgNPs are bona fide anticancer agents that act in a p53-dependent manner. Original submitted 16 March 2012; Revised submitted 25 August 2012; Published online 21 March 2013.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • DNA Damage / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • HCT116 Cells
  • Humans
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry
  • NF-kappa B / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Silver / administration & dosage*
  • Silver / chemistry
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Silver
  • Caspase 3