Metallothionein and Superoxide Dismutase—Antioxidative Protein Status in Fullerene-Doxorubicin Delivery to MCF-7 Human Breast Cancer Cells

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.

Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model

“…Literature data reported SOD1 overexpression in malignant BC cells, and the development of novel drug complexes targeting SOD activity can be considered as a promising strategy in the chemotherapy of malignant tumors [65]. In the present study, a similar SOD1 immunoreactivity was measured both in pulmonary parenchyma and metastases comparing M. U-care-treated and untreated animals, suggesting that Micotherapy U-care blend supplementation before tumor cells injection and throughout the following experimental time, seemed to not affect SOD1 expression pattern during tumor progression, until death.…”

Interplay between Carbonic Anhydrases and Metallothioneins: Structural Control of Metalation

“…Metallothioneins are key players in the detoxification of Cd 2+ in mammals, but the concentration and accumulation of Cd-MT in the kidneys for decades eventually leads to necrosis and kidney failure [ 104 ]. Currently, MTs are known to interfere with platinum-based anticancer drugs and doxorubicin treatment of breast cancer [ 105 ]. In vitro studies show MTs binding to xenobiotic metal drugs cisplatin [ 106 , 107 , 108 ] and therapeutically relevant ruthenium and rhodium complexes in unusually anarchistic ways [ 39 , 109 , 110 , 111 ].…”

Carbon Based Nanodots in Early Diagnosis of Cancer

“…Fullerenes act as immunomodulators and activate various immune cells by generating reactive oxygen species (ROS), thus killing cancer cells. Fullerenes also overcome tumor resistance to chemotherapeutic drugs and its derivatives are used as antioxidant species ( Kepinska et al, 2018 ; Sergeeva et al, 2019 ). A study involving anti-cancer drug conjugated to C 60 fullerene showed C 60 to trigger phagocyte activity.…”