C(60) Fullerene as Synergistic Agent in Tumor-Inhibitory Doxorubicin Treatment

BACKGROUND: Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C(60) fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Dox. OBJECTIVE: The aim of this study was to estimate the antitumor effect and antioxidant enzyme activity of combined C(60) fullerene and Dox (C(60) + Dox) in the liver and heart of mice with Lewis lung carcinoma compared with Dox treatment alone. METHODS: Highly stable pristine C(60) fullerene aqueous colloid solution (concentration 1.0 mg/ml, average hydrodynamic diameter of nanoparticles 50 nm) was used in the study and characterized by means of atomic force microscopy (AFM). The in vivo investigation of C(60)-Dox action was performed via the standard methods of histological and enzyme activity analyses. RESULTS: Dox (total dose 2.5 mg/kg) combined with C(60) fullerene (total dose 25 mg/kg) in tumor-bearing animals resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone. C(60) fullerene demonstrated a protective effect against superoxide dismutase and glutathione peroxidase inhibition induced by Dox-dependent oxidative insult in the liver and heart. CONCLUSION: Combined treatment with C(60) + Dox is considered to be a promising approach for cancer chemotherapy.