Remodulating effect of doxorubicin on the state of iron-containing proteins, and redox characteristics of tumor with allowance for its sensitivity to cytostatic agents

Ukr Biochem J. 2016 Jan-Feb;88(1):99-108. doi: 10.15407/ubj88.01.099.

Abstract

The study was aimed at determining the changes of metal-containing proteins in blood serum and tumor tissue of animals with parental and doxorubicin-resistant strains of Walker-256 carcinosarcoma before and after the cytostatic administration. It has been shown that upon doxorubicin action the levels of total iron and transferrin in the tissues from the both groups of animals decreased while that of ferritine simultaneously increased with more pronounced pattern in the group of animals with resistant tumor strain. It has been shown that upon the action of doxorubicin in tumor tissue of animals with different sensitivity to the cytostatic there could be observed oppositely directed changes in the redox state of these cells that in turn determined the content of “ free iron” complexes, RO S generation and concentration of active forms of matrix metaloproteinase- 2 and matrix metaloproteinase-9, namely, the increase of these indexes in animals with parental strain and their decrease in animals with the resistant one. So, our study has demonstrated the remodulating effect of doxorubicin on the state of metal-containing proteins and redox characteristics of tumor dependent on its sensitivity to cytostatic, at the levels of the tumor and an organism. These data may serve as a criterion for the development of programs for the correction of malfunction of iron metabolism aimed at elevating tumor sensitivity to cytostatic agents.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Carcinoma 256, Walker / drug therapy*
  • Carcinoma 256, Walker / genetics
  • Carcinoma 256, Walker / metabolism
  • Carcinoma 256, Walker / pathology
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Ferritins / genetics
  • Ferritins / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Iron / metabolism*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Transplantation
  • Rats
  • Rats, Inbred Strains
  • Reactive Oxygen Species / metabolism
  • Transferrin / genetics
  • Transferrin / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Reactive Oxygen Species
  • Transferrin
  • Doxorubicin
  • Ferritins
  • Iron
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat