Dual-target cancer theranostic for glutathione S-transferase and hypoxia-inducible factor-1α inhibition

Chem Commun (Camb). 2017 Nov 16;53(92):12406-12409. doi: 10.1039/c7cc08162f.

Abstract

We developed a dual-target theranostic F671, which could exhibit synergetic anticancer effects for inhibiting the activities of glutathione S-transferase and the accumulation of hypoxia inducible factor-1α. F671 undergoes self-immolative cleavage when exposed to GSTP1-1 in live cancer cells, facilitating the visualization of molecule release and distribution, as well as confirming the autophagy-induced apoptosis.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Autophagy
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / drug therapy
  • Cell Line, Tumor
  • Female
  • Glutathione S-Transferase pi / antagonists & inhibitors*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Intracellular Membranes / drug effects
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / drug therapy
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / metabolism
  • Oxadiazoles / pharmacology*
  • Oxadiazoles / therapeutic use
  • Prodrugs / chemical synthesis
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use
  • Theranostic Nanomedicine

Substances

  • Antineoplastic Agents
  • HIF1A protein, human
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxadiazoles
  • Prodrugs
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Gstp1 protein, mouse