Synergistic Antitumor Effect of Oligogalacturonides and Cisplatin on Human Lung Cancer A549 Cells

Int J Mol Sci. 2018 Jun 14;19(6):1769. doi: 10.3390/ijms19061769.

Abstract

Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.

Keywords: adjuvant therapy; cisplatin; oligogalacturonides; synergistic effect.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Drug Synergism
  • HEK293 Cells
  • Humans
  • Oligosaccharides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Oligosaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • oligogalacturonic acid
  • Caspase 3
  • Cisplatin