Repurposing the anti-malarial drug, quinacrine: new anti-colitis properties

Oncotarget. 2016 Aug 16;7(33):52928-52939. doi: 10.18632/oncotarget.10608.

Abstract

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with an increased risk of colorectal cancer in 8-10 years after disease onset. Current colitis treatment strategies do not offer a cure for the disease, but only treat the symptoms with limited success and dangerous side-effects. Also, there is no preventive treatment for either UC or colorectal cancer. Quinacrine is an anti-malarial drug with versatile use in the treatment of diseases involving inflammatory response such as rheumatoid arthritis and lupus erythematosus. It also has putative anti-cancer effect. Quinacrine's anti-inflammatory, anti-oxidant properties, and anti-tumorigenic properties make it a potential small molecule preventive agent for both UC and associated colorectal cancer.

Results: There were obvious changes in the CDI, histology, and inflammatory load in quinacrine-treated groups in a dose and time dependent manner in both models of UC, induced by chemical or haptenating agent.

Materials and methods: We tested quinacrine at two different doses as a colitis treatment agent in two mouse models of UC - the dextran sulfate sodium and oxazolone. The clinical disease index (CDI), histological changes of the colon, levels of inflammatory markers (Cox-2, iNOS, p53) and overall health vitals were evaluated.

Conclusions: We demonstrate that quinacrine successfully suppresses colitis without any indication of toxicity or side-effects in two mouse models of UC.

Keywords: colitis; dextran sulfate sodium; inflammation; oxazolone; quinacrine.

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Cell Line
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Cyclooxygenase 2 / metabolism
  • Dextran Sulfate
  • Disease Models, Animal
  • Drug Repositioning*
  • Humans
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Oxazolone
  • Quinacrine / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antimalarials
  • Tumor Suppressor Protein p53
  • Oxazolone
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Quinacrine