Inhibition of aldehyde dehydrogenase by furazolidone nanoemulsion to decrease cisplatin resistance in lung cancer cells

Ther Deliv. 2021 Aug;12(8):611-625. doi: 10.4155/tde-2020-0130. Epub 2021 Jul 21.

Abstract

Aim: The overexpression of aldehyde dehydrogenase (ALDH) in cancer cells contributes to therapeutic resistance. Furazolidone (FUR) is a strong ALDH inhibitor. Methods: FUR nanoemulsion (NE) was formulated and tested for ALDH inhibitory activity in comparison with free FUR. The cytotoxic potential of cisplatin was evaluated in combination with free FUR and FUR NE. Results: The optimized FUR NE showed droplet size of 167.9 ± 3.1 nm and drug content of 84.2 ± 2.3%. FUR NE inhibited 99.75 ± 2.1% of ALDH activity while 25.0 ± 4.6% was inhibited by free FUR. FUR NE increased the sensitivity to cisplatin in A549 cells by more than tenfold by its ALDH inhibitory effects. Conclusion: This finding can be a promising approach to improve cancer survival in ALDH-positive drug-resistant cancers.

Keywords: Furazolidone; aldehyde dehydrogenase; cisplatin; nanoemulsion; sensitivity.

MeSH terms

  • A549 Cells
  • Aldehyde Dehydrogenase / antagonists & inhibitors*
  • Cell Line, Tumor
  • Cisplatin* / pharmacology
  • Drug Resistance, Neoplasm
  • Furazolidone / pharmacology*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Nanostructures

Substances

  • Furazolidone
  • Aldehyde Dehydrogenase
  • Cisplatin