%0 journal article
%@ 1998-0124
%A Prylutska, S.,Panchuk, R.,Golunski, G.,Skivka, L.,Prylutskyy, Y.,Hurmach, V.,Skorohyd, N.,Borowik, A.,Woziwodzka, A.,Piosik, J.,Kyzyma, O.,Haramus, V.M.,Bulavin, L.,Evstigneev, M.,Buchelnikov, A.,Stoika, R.,Berger, W.,Ritter, U.,Scharff, P.

%D 2017
%J Nano Research
%N 2
%P 652-671 
%R doi:10.1007/s12274-016-1324-2
%T C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance
%U https://doi.org/10.1007/s12274-016-1324-2
2 
%X We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C60 fullerene (C60+Cis complex) and showed its higher toxicity toward tumor cell lines in vitro when compared to Cis alone. The highest toxicity of the complex was observed in HL-60/adr and HL-60/vinc chemotherapy-resistant human leukemia cell sublines (resistant to Adriamycin and Vinculin, respectively). We discovered that the action of the C60+Cis complex is associated with overcoming the drug resistance of the tumor cell lines through observing an increased number of apoptotic cells in the Annexin V/PI assay. Moreover, in vivo assays with Lewis lung carcinoma (LLC) C57BL/6J male mice showed that the C60+Cis complex increases tumor growth inhibition, when compared to Cis or C60 fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C60 fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP-1), and multidrug resistance protein 2 (MRP-2) molecules. The observed phenomenon revealed a possible mechanism to bypass tumor cell drug resistance by the C60+Cis complex. Additionally, the results of the Ames test show that the formation of such a complex diminishes the Cis mutagenic activity and may reduce the probability of secondary neoplasm formation. In conclusion, the C60+Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo, overcoming drug resistance likely by the potential of the C60 fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C60+Cis complex might be a potential novel chemotherapy modification.