@misc{prylutska_c60_fullerene_2017, author={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.}, title={C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance}, year={2017}, howpublished = {journal article}, doi = {https://doi.org/10.1007/s12274-016-1324-2}, abstract = {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.}, note = {Online available at: \url{https://doi.org/10.1007/s12274-016-1324-2} (DOI). Prylutska, S.; Panchuk, R.; Golunski, G.; Skivka, L.; Prylutskyy, Y.; Hurmach, V.; Skorohyd, N.; Borowik, A.; Woziwodzka, A.; Piosik, J.; Kyzyma, O.; Haramus, V.; Bulavin, L.; Evstigneev, M.; Buchelnikov, A.; Stoika, R.; Berger, W.; Ritter, U.; Scharff, P.: C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance. Nano Research. 2017. vol. 10, no. 2, 652-671. DOI: 10.1007/s12274-016-1324-2}}