Biochemical action of new complexes of ruthenium with quinolones as potential antitumor agents

Anticancer Res. 2015 Jun;35(6):3371-8.

Abstract

Background: The aim of the present study paper was to identify the role of reactive oxygen species (ROS) in apoptosis signaling mechanisms. We used for this purpose two ruthenium complex compounds based on that overproduce these reactive species by their metabolism thus manifesting their antitumor activity too.

Materials and methods: In vivo studies were performed in Walker 256 carcinoma-bearing Wistar rats treated with two ruthenium (III) (Ru(III)) complexes with -fluoroquinolones norfloxacin and ofloxacin. The treatment started 7 days after tumor grafting. We assayed the dynamics of apoptosis by flow-cytometry and the biochemical oxidative status parameters. The biological samples used were serum and whole-tumor tissues; the results were compared to the untreated control group.

Results: The results showed an increase of apoptosis from 14.79% to 59.72% 14.79% to 59.72% in tumor cells treated with the most active combination, ruthenium complex with norfloxacin. We also noted an increase of the oxidative status and ROS production during treatment.

Conclusion: The newly-synthesized complexes are less toxic and their activity is based on the induction of oxidative stress.

Keywords: Oxidative stress; anticancer treatment; ruthenium complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Carcinoma 256, Walker / drug therapy*
  • Carcinoma 256, Walker / metabolism
  • Carcinoma 256, Walker / pathology
  • Flow Cytometry
  • Humans
  • Quinolones / administration & dosage*
  • Quinolones / chemical synthesis
  • Quinolones / chemistry
  • Rats
  • Reactive Oxygen Species / metabolism
  • Ruthenium / administration & dosage*
  • Ruthenium / chemistry
  • Signal Transduction / drug effects

Substances

  • Quinolones
  • Reactive Oxygen Species
  • Ruthenium