Arsenene: A Potential Therapeutic Agent for Acute Promyelocytic Leukaemia Cells by Acting on Nuclear Proteins

Angew Chem Int Ed Engl. 2020 Mar 23;59(13):5151-5158. doi: 10.1002/anie.201913675. Epub 2020 Feb 3.

Abstract

Arsenene has recently emerged as a promising new two-dimensional material for biomedical applications because of its excellent optical and electronic properties. Herein, novel 2D arsenene nanosheets were synthesized and shown to be effective against NB4 promyelocytic leukaemia (APL) cells (82 % inhibition) as well as inducing apoptosis while showing no toxicity towards normal cells. The high zeta potential, small size, and the planar structure were crucial to the toxicity of the materials. Label-free proteomic profiling analysis suggested that arsenene affected nuclear DNA replication, nucleotide excision repair, and pyrimidine metabolism pathways by downregulating the DNA polymerases POLE, POLD1, POLD2, and POLD3. Mass spectrometric studies showed that arsenene bound mainly to nuclear nucleotide acid binding proteins in NB4 cells and further cellular fluorescence studies revealed that the arsenene destroyed the nuclei. In vivo toxicity tests in mice also indicated the physiological biosafety of arsenene.

Keywords: antitumor agents; apoptosis; arsenene; nuclear proteins; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Arsenicals / chemistry*
  • Arsenicals / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • DNA Repair / drug effects
  • DNA Replication / drug effects
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Nanoparticles / chemistry*
  • Nuclear Proteins / metabolism
  • Proteomics
  • Pyrimidines / metabolism
  • Thioredoxins / genetics
  • Thioredoxins / metabolism

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Nuclear Proteins
  • Pyrimidines
  • TXNL1 protein, human
  • Thioredoxins
  • DNA-Directed DNA Polymerase
  • pyrimidine