No abstract

The development of resistance of cancer cells to therapeutic agents is the major obstacle in the successful treatment of breast cancer and the main cause of breast cancer recurrence. The results of several studies have demonstrated an important role of altered cellular iron metabolism in the progression of breast cancer and suggested that iron metabolism may be involved in the acquisition of a cancer cell drug-resistant phenotype. In the present study, we show that human MCF-7 breast cancer cells with an acquired resistance to the chemotherapeutic drugs doxorubicin (MCF-7/DOX) and cisplatin (MCF-7/CDDP) exhibited substantial alterations in the intracellular iron content and levels of iron-regulatory proteins involved in the cellular uptake, storage and export of iron, especially in profoundly increased levels of ferritin light chain (FTL) protein. The increased levels of FTL in breast cancer indicate that FTL may be used as a diagnostic and prognostic marker for breast cancer. Additionally, we demonstrate that targeted downregulation of FTL protein by the microRNA miR-133a increases sensitivity of MCF-7/DOX and MCF-7/CDDP cells to doxorubicin and cisplatin. These results suggest that correction of iron metabolism abnormalities may substantially improve the efficiency of breast cancer treatment.

Growth experiments of transplanted malignant tumors in the presence of water-soluble C60 fullerenes were performed on groups of mice. It was found that C60 fullerenes efficiently inhibit the growth of transplanted malignant tumors. This behavior can be explained through their high antioxidant activity and the blocking of the specific cell receptors (for example, endothelial growth factor). The findings demonstrate the possibility of using C60 fullerenes in anticancer therapy.

An increase of the intracellular reactive oxygen species (ROS) concentration leads to the development of oxidative stress and, thus, to the damage of cell components. The cause-and-effect relations between these processes have not been fully established yet. The ability of photo excited supramolecular composites containing fullerenes C60 immobilized at nanosilica particles to generate reactive oxygen species (ROS) in cells of two types (rat thymocytes, and transformed cells of ascite Erlich carcinoma, EAC, and leucosis L1210) is demonstrated. The damaging effect of photo excited C60-composites are shown, which appeared to be selective and manifested in transformed cells, but not in thymocytes. It has been shown that after the irradiation of aqueous solutions or cell suspensions in the presence of fullerene C60, the generation of reactive oxygen species is observed. It has been shown that the influence of photo excited fullerene C60 on metabolic processes depends on the composition of C60-containing complex and on the type of the cells. The damaging effects of photo excited fullerene C60-containing composites were demonstrated to be selective. The data presented suggest that the application of fullerene C60-containing composites for the selective activation of ROS-dependent death program in certain types of tumor cells is very promising.