Tag Archives: ceruloplasmin

The concentration of ceruloplasmin in blood of tumor-bearing rats after administration of a dirhenium(III) compound and cisplatin

O. I. Hrabovska1, K. L. Shamelashvili2, O. V. Shtemenko4, N. I. Shtemenko3,4

1Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine, Dnipro;
2SI “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro;
3Dnipro University of Technology, Ukraine;
4Ukrainian State University of Chemical Technology, Dnipro;
e-mail: n.shtemenko@i.ua

Received: 18 January 2019; Accepted: 18 October 2019

Contemporary investigations of mechanisms of resistance to platinides showed the key role of copper metabolism in cancer patients and proposed possible methods to attenuate the resistance by modulation of copper transporting mechanisms. In this vein, investigation of ceruloplasmin (Cp) levels – the main copper-containing protein in blood, in experiments with tumor-containing animals upon cytostatics administration is topical and has great importance. The concentration of Cp was measured in the serum of tumor-bearing rats with ordinary (T8) and resistant to cisplatin (T8*) Guerin’s carcinoma upon administration of cisplatin and quadruple bonding dirhenium(III) compound dichlorotetra-μ-isobutyratodirhenium(ІІІ) (I) in different medicamental forms. It was shown that development of tumor in T8 group led to increasing of concentration of Cp in 3.7 times and in T8* group – more than in 8 times in comparison to control, confirming the essential role of Cp in the formation of resistance phenomenon. Administration of cisplatin together with I led to effective inhibition of tumor in groups with T8 and T8*, indicating decreased resistance in the group T8*. Greater reduction of Cp levels was observed in the groups with T8* upon administration of the rhenium-plati­num antitumor system, than in groups with T8, that underlines the importance of further investigations of the dirhenium(III) compounds in the resistance to cytostatics cancer models. Some mechanisms concerning the regulation of copper homeostasis and properties of nano-composites are discussed.

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

V. F. Chekhun, Yu. V. Lozovska, A. P. Burlaka,
I. I. Ganusevich, Yu. V. Shvets, N. Yu. Lukyanova,
I. M. Todor, N. A. Tregubova, L. A. Naleskina

R. E. Kavetsky Institute of Experimental Pathology, Oncology
and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
e-mail: Lozovskaya.2012@mail.ru

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, ROS 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.

Laureates of the Palladin Prize of the National Academy of Sciences of Ukraine (1989–1990)

R. P. Vynogradova, V. M. Danilova

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua

In 1989 N. K. Berdinskikh and S. P. Zaletok received the Palladin Prize of NAS of Ukraine for the monograph “Polyamines and tumor growth” and in1990 A. M. Belous, V. A. Bondarenko and O. K. Gulevsky were awarded the prize for the series of works “Studies of the mechanisms of cryoinjury of biological membranes” and the monograph “Biomembrane barrier properties at low temperatures”.

Metalloproteins during development of Walker-256 carcinosarcoma resistant phenotype

V. F. Chekhun, Yu. V. Lozovska, A. P. Burlaka, I. I. Ganusevich,
Yu. V. Shvets, N. Yu. Lukianova, I. M. Todor, D. V. Demash,
A. A. Pavlova, L. A. Naleskina

R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
e-mial: Lozovskaya.2012@mail.ru

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development of doxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carcinosarcoma tissue. We observed decreased serum ferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases with fully developed resistance phenotype. Transferrin content showed changes opposite to that of ferritin. During the development of resistance phenotype the tumor tissue also exhibited increased ‘free iron’ concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein  thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.