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

• Published in: Ukrainian biochemical journal Vol. 88; no. 1; pp. 99 - 108
• Main Authors: Chekhun, V F, Lozovska, Yu V, Burlaka, A P, Ganusevich, L I, Shvets, Yu V, Lukyanova, N Yu, Todor, I M, Tregubova, N A, Naleskina, L A
• Format: Journal Article
• Language: English
• Published: Ukraine National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 01-01-2016
• Subjects: 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
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj88.01.099

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.