Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin

Biochem Biophys Res Commun. 2016 Jan 8;469(2):164-70. doi: 10.1016/j.bbrc.2015.11.088. Epub 2015 Nov 23.

Abstract

Recently, targeting deregulated energy metabolism is an emerging strategy for cancer therapy. In the present study, combination of DCA and metformin markedly induced cell death, compared with each drug alone. Furthermore, the expression levels of glycolytic enzymes including HK2, LDHA and ENO1 were downregulated by two drugs. Interestingly, HIF-1α activation markedly suppressed DCA/metformin-induced cell death and recovered the expressions of glycolytic enzymes that were decreased by two drugs. Based on these findings, we propose that targeting HIF-1α is necessary for cancer metabolism targeted therapy.

Keywords: Cancer metabolism; Dichloroacetate; Glycolytic enzymes; HIF-1α; Metformin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Dichloroacetic Acid / administration & dosage*
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MCF-7 Cells
  • Metformin / administration & dosage*
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Treatment Outcome

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Metformin
  • Dichloroacetic Acid