(-)-Epicatechin enhances etoposide-induced antileukaemic effect in rats with acute myeloid leukaemia

Anticancer Res. 2012 Jul;32(7):2905-13.

Abstract

Background: (-)-Epicatechin (EC) is a naturally occurring compound which induces oxidative DNA damage in human acute myeloid leukaemia (AML) cells.

Aim: The aim of the study was to examine the influence of EC on the antileukaemic effect of etoposide in rats with AML.

Materials and methods: Brown Norway rats with AML were treated with EC for 23 days and etoposide was administered for the last three days of the experiment. Bone marrow and splenic cell apoptosis was investigated by flow cytometry using annexin V-allophycocyanin staining. The oxidative status was investigated in homogenates of the liver.

Results: EC was found to increase the in vivo apoptotic effect of etoposide resulting in the decrease of the percentage of leukaemia cells in EC-treated rats in comparison to those treated with etoposide only. Investigation of malondialdehyde and ferric ion-reducing ability of plasma levels indicated that EC increases the oxidative stress induced by etoposide in leukaemic rats.

Conclusion: EC can enhance the antileukaemia properties of etoposide in vivo through augmentation of oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Catechin / administration & dosage
  • Catechin / pharmacology*
  • Drug Synergism
  • Etoposide / administration & dosage
  • Etoposide / pharmacology*
  • Fluorescence Recovery After Photobleaching
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred BN
  • Spleen / drug effects
  • Spleen / pathology
  • Superoxide Dismutase / metabolism

Substances

  • Malondialdehyde
  • Etoposide
  • Catechin
  • Superoxide Dismutase