A novel biocompatible formate bridged 1D-Cu(ii) coordination polymer induces apoptosis selectively in human lung adenocarcinoma (A549) cells

Dalton Trans. 2021 Feb 14;50(6):2253-2267. doi: 10.1039/d0dt03782f. Epub 2021 Jan 28.

Abstract

Copper compounds are promising candidates for next-generation metal anticancer drugs. Therefore, we synthesized and characterized a formate bridged 1D coordination polymer [Cu(L)(HCOO)2]n, (L = 2-methoxy-6-methyl-3-((quinolin-8-ylimino)methyl)chroman-4-ol), PCU1, wherein the Cu(ii) center adopts a square pyramidal coordination environment with adjacent CuCu distances of 5.28 Å. Primarily, in vitro DNA interaction studies revealed a metallopolymer which possesses high DNA binding propensity and cleaves DNA via the oxidative pathway. We further analysed its potential on cancerous cells MCF-7, HeLa, A549, and two non-tumorigenic cells HEK293 and HBE. The selective cytotoxicity potential of PCU1 against A549 cells driven us to examine the mechanistic pathways comprehensively by carrying out various assays viz, cell cycle arrest, Annexin V-FTIC/PI assay, autophagy, intercellular localization, mitochondrial membrane potential 'MMP', antiproliferative assay, and gene expression of TGF-β and MMP-2.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromones* / chemistry
  • Chromones* / pharmacology
  • Coordination Complexes* / chemistry
  • Coordination Complexes* / pharmacology
  • Copper* / chemistry
  • Copper* / pharmacology
  • DNA / chemistry
  • DNA Cleavage
  • Humans
  • Lung Neoplasms / drug therapy*
  • Matrix Metalloproteinase 2 / genetics
  • Membrane Potential, Mitochondrial / drug effects
  • Transforming Growth Factor beta / genetics

Substances

  • Antineoplastic Agents
  • Chromones
  • Coordination Complexes
  • Transforming Growth Factor beta
  • Copper
  • DNA
  • calf thymus DNA
  • MMP2 protein, human
  • Matrix Metalloproteinase 2