S-Dimethylarsino-glutathione (darinaparsin®) targets histone H3.3, leading to TRAIL-induced apoptosis in leukemia cells

Chem Commun (Camb). 2019 Oct 29;55(87):13120-13123. doi: 10.1039/c9cc07605k.

Abstract

Histone H3.3 was identified as an arsenic-binding protein of S-dimethylarsino-glutathione (ZIO-101, darinaparsin®) in leukemia cells by GE-ICP-MS. Such a binding results in TRAIL-induced apoptosis. We further validate histone H3.3 as a vital target for ZIO-101, offering new information on the mode of action of arsenic-based anticancer agents.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenicals / chemistry
  • Arsenicals / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Glutathione / analogs & derivatives*
  • Glutathione / chemistry
  • Glutathione / pharmacology
  • Histones / antagonists & inhibitors*
  • Histones / metabolism
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / pathology
  • Molecular Structure
  • TNF-Related Apoptosis-Inducing Ligand / antagonists & inhibitors*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Histones
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • darinaparsin
  • Glutathione