Abstract
Doxorubicin (DOX) is one of the most frequently used anticancer drugs in breast cancer treatment. However, clinical applications of DOX are restricted, largely due to the fact that its action disturbs the pro/antioxidant balance in both cancerous and non-cancerous cells. The aim of this study was to investigate the influence of fullerene (C60) in cell treatment by DOX on the proliferation of human breast cancer cells (MCF-7), concentration of metallothionein (MT) and superoxide dismutase (SOD), and SOD activity in these cells. The use of C60 in complexes with DOX causes a change in the level of cell proliferation of about 5% more than when caused by DOX alone (from 60–65% to 70%). The use of C60 as a DOX nanotransporter reduced the MT level increase induced by DOX. C60 alone caused an increase of SOD1 concentration. On the other hand, it led to a decrease of SOD activity. C60 in complex with DOX caused a decrease of the DOX-induced SOD activity level. Exposure of MCF-7 cells to DOX-C60 complexes results in a decrease in viable cells and may become a new therapeutic approach to breast cancer. The effects of C60 in complexes with DOX on MCF-7 cells included a decreased enzymatic (SOD activity) and nonenzymatic (MT) antioxidant status, thus indicating their prooxidant role in MCF-7 cells.
Highlights
Breast cancer is the most commonly diagnosed cancer in women worldwide and the leading cause of mortality in American women [1]
The goals of the present study were to determine the level of the MT-1/2 and SOD1 as well as Zn/Cu superoxide dismutase (SOD) activity in the MCF-7 cell line when the cells were exposed to DOX alone and in complexes with C60 as nanotransporters and antioxidants selected to protect the body from the effects of DOX therapy
It has been shown that the administration of fullerene derivative Gd@C82(OH)22 significantly impairs the process of angiogenesis in tumor cells, reducing blood perfusion and nutrition of the entire tumor mass [28]
Summary
Breast cancer is the most commonly diagnosed cancer in women worldwide and the leading cause of mortality in American women [1]. Free radicals, operating on a variety of signal pathways, increase the expression of proteins responsible for increasing the number of cell divisions [3]. This action results in increased cell proliferation and tumor mass growth [4]. Anthracyclines (comprising doxorubicin) are regularly used in breast cancer treatment [5,6]. Doxorubicin (DOX) is a DNA interchelator which inhibits topoisomerase II, thereby inhibiting cancer cell growth. DOX can be converted by reductases to anthracycline semiquinone free radicals. In aerobic conditions, they are able to reduce molecular oxygen to O2− and H2O2. One strategy to mitigate the side effects of DOX is the use of drug delivery systems [7]
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