HIF-1α decoy oligodeoxynucleotides inhibit HIF-1α signaling and breast cancer proliferation

Int J Oncol. 2015 Jan;46(1):215-22. doi: 10.3892/ijo.2014.2715. Epub 2014 Oct 21.

Abstract

Although HIF-1α is considered an attractive target for the development of cancer therapies, like other transcriptional factors, it has been regarded as 'undruggable'. The decoy approach is a new class of antigene strategy that can be used to modulate the function of endogenous transcriptional factors. Here, we designed a decoy oligodeoxynucleotide (ODN) and tested its effect on the function of HIF-1α. We found the HIF-1α decoy ODN could efficiently enter into cells. Furthermore, these decoy ODNs can significantly block the expression of VEGFA, a known targeted gene of HIF-1α suggesting that the HIF-1α decoy ODNs can inhibit the function of HIF-1α. More importantly, the HIF-1α decoy ODN induced apoptosis and cell cycle arrest in MDA-MB-231 breast cancer cells. In summary, HIF-1α decoy ODNs can inhibit the function of HIF-1α and induce cancer cell apoptosis. Therefore, HIF-1α decoy ODNs should be further modified to improve their biological activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Oligodeoxyribonucleotides / pharmacology*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oligodeoxyribonucleotides
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A