Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines

Cis-dichlorodiammineplatinum (II), commonly known as cisplatin, is a widely used anticancer drug. However, the therapeutic efficacy of the drug is limited due to various dose-limiting side effects and development of acquired resistance. The resistance of malignant cells to cisplatin may be connected...

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Main Authors: H. Falfushynska, Y. Filyak, O. Stoliar, R. Stoika
Format: Article
Language:English
Published: Львівський національний університет імені Івана Франка 2012-12-01
Series:Біологічні студії
Subjects:
Online Access:http://publications.lnu.edu.ua/journals/index.php/biology/article/view/328
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spelling doaj-8ca1689f5c8f41baba0cf3581f5c74542021-08-02T15:31:43ZengЛьвівський національний університет імені Івана ФранкаБіологічні студії1996-45362311-07832012-12-016351410.30970/sbi.0603.251Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell linesH. Falfushynska0https://orcid.org/0000-0003-3058-4919Y. Filyak1O. Stoliar2https://orcid.org/0000-0002-8579-2881R. Stoika3https://orcid.org/0000-0001-5719-2187Volodymyr Hnatiuk Ternopil National Pedagogical University, Research Laboratory of Comparative Biochemistry and Molecular Biology, UkraineInstitute of Cell Biology, NAS of UkraineVolodymyr Hnatiuk Ternopil National Pedagogical University, Research Laboratory of Comparative Biochemistry and Molecular Biology, UkraineInstitute of Cell Biology of NAS of UkraineCis-dichlorodiammineplatinum (II), commonly known as cisplatin, is a widely used anticancer drug. However, the therapeutic efficacy of the drug is limited due to various dose-limiting side effects and development of acquired resistance. The resistance of malignant cells to cisplatin may be connected to elevated concentration of cellular thiols. To verify this hypotheses, we compared the concentrations of low weight cellular thiols, metallothionein (MT) and glutathione (reduced, GSH and oxidized, GSSG) and also the metal-binding properties of MT in the two cell lines, known to be resistant (L1210R) or sensitive (L1210S) to cisplatin. It was established that R-cells were characterised by hi­gher concentrations of MTs and GSH, higher ratio of copper in the composition of MTs in comparison to zinc than S-cells. The treatment by cisplatin provoked the decrease of the GSSG concentration only in the S-cells without the changes in GSH concentration. Hence, R-cells insensitivity to cisplatin can be related to higher levels of MTs and GSH. Reported for the first time peculiar metal composition of MTs in R-cells can also give an advance to these cells by particular oxidizing properties of copper-MT. These specific characteristics of thiols in malignant cells could be useful for the indication of cisplatin resistance.http://publications.lnu.edu.ua/journals/index.php/biology/article/view/328cisplatinresistansemetallothioneinglutathionecopper
collection DOAJ
language English
format Article
sources DOAJ
author H. Falfushynska
Y. Filyak
O. Stoliar
R. Stoika
spellingShingle H. Falfushynska
Y. Filyak
O. Stoliar
R. Stoika
Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
Біологічні студії
cisplatin
resistanse
metallothionein
glutathione
copper
author_facet H. Falfushynska
Y. Filyak
O. Stoliar
R. Stoika
author_sort H. Falfushynska
title Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
title_short Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
title_full Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
title_fullStr Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
title_full_unstemmed Study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia L1210 cell lines
title_sort study of interrelations between resistance to cisplatin and composition of low molecular weight thiols in murine leukemia l1210 cell lines
publisher Львівський національний університет імені Івана Франка
series Біологічні студії
issn 1996-4536
2311-0783
publishDate 2012-12-01
description Cis-dichlorodiammineplatinum (II), commonly known as cisplatin, is a widely used anticancer drug. However, the therapeutic efficacy of the drug is limited due to various dose-limiting side effects and development of acquired resistance. The resistance of malignant cells to cisplatin may be connected to elevated concentration of cellular thiols. To verify this hypotheses, we compared the concentrations of low weight cellular thiols, metallothionein (MT) and glutathione (reduced, GSH and oxidized, GSSG) and also the metal-binding properties of MT in the two cell lines, known to be resistant (L1210R) or sensitive (L1210S) to cisplatin. It was established that R-cells were characterised by hi­gher concentrations of MTs and GSH, higher ratio of copper in the composition of MTs in comparison to zinc than S-cells. The treatment by cisplatin provoked the decrease of the GSSG concentration only in the S-cells without the changes in GSH concentration. Hence, R-cells insensitivity to cisplatin can be related to higher levels of MTs and GSH. Reported for the first time peculiar metal composition of MTs in R-cells can also give an advance to these cells by particular oxidizing properties of copper-MT. These specific characteristics of thiols in malignant cells could be useful for the indication of cisplatin resistance.
topic cisplatin
resistanse
metallothionein
glutathione
copper
url http://publications.lnu.edu.ua/journals/index.php/biology/article/view/328
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