Skip to main content

C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance

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.

This is a preview of subscription content, access via your institution.

References

  1. Corrie, P. G. Cytotoxic chemotherapy: Clinical aspects. Medicine 2008, 36, 24–28.

    Article  Google Scholar 

  2. de Vita, V. T.; Hellman, S.; Rosenberg, S. A. Principles and Practice of Oncology; 6th ed.; Lippincott, Williams & Wilkins: Philadelphia, 2001.

  3. Hirsch, J. An anniversary for cancer chemotherapy. JAMA 2006, 296, 1518–1520.

    Article  Google Scholar 

  4. Florea, A. M.; Busselberg, D. Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel) 2011, 3, 1351–1371.

    Article  Google Scholar 

  5. Huynh, V. T.; Scarano, W.; Stenzel, M. H. Drug delivery systems for platinum drugs. In Nanopharmaceutics. Liang, X. J., Eds.; World Scientific Publishing Co. Pte. Ltd.: Singapore, 2012; pp 201–241.

    Chapter  Google Scholar 

  6. Carmona, R.; Liang, X.-J. Improving platinum efficiency: Nanoformulations. In Nanopharmaceutics. Liang, X. J., Eds.; World Scientific Publishing Co. Pte. Ltd.: Singapore, 2012; pp 243–274.

    Chapter  Google Scholar 

  7. Liu, L.; Ye, Q.; Lu, M.; Lo, Y. C.; Hsu, Y. H.; Wei, M. C.; Chen, Y. H.; Lo, S. C.; Wang, S. J.; Bain, D. J. et al. A new approach to reduce toxicities and to improve bioavailabilities of platinum-containing anti-cancer nanodrugs. Sci. Rep. 2015, 5, 10881.

    Article  Google Scholar 

  8. Dong, X. P.; Xiao, T. H.; Dong, H.; Jiang, N.; Zhao, X. G. Endostar combined with cisplatin inhibits tumor growth and lymphatic metastasis of Lewis lung carcinoma xenografts in mice. Asian Pac. J. Cancer Prev. 2013, 14, 3079–3083.

    Article  Google Scholar 

  9. Yu, H. Y.; Tang, Z. H.; Li, M. Q.; Song, W. T.; Zhang, D. W.; Zhang, Y.; Yang, Y.; Sun, H.; Deng, M. X.; Chen, X. S. Cisplatin loaded poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for potential cancer therapy: Preparation, in vitro and in vivo evaluation. J. Biomed. Nanotechnol. 2016, 12, 69–78.

    Article  Google Scholar 

  10. Cataldo, F.; Da Ros, T. Medicinal Chemistry and Pharmacological Potential of Fullerenes and Carbon Nanotubes; Springer: Amsterdam, 2008.

  11. Andrievsky, G.; Klochkov, V.; Derevyanchenko, L. Is the C60 fullerene molecule toxic?! Fullerenes, Nanotubes, Carbon Nanostruct. 2005, 13, 363–376.

    Article  Google Scholar 

  12. Prylutska, S. V.; Matyshevska, O. P.; Golub, A. A.; Prylutskyy, Y. I.; Potebnya, G. P.; Ritter, U.; Scharff, P. Study of C60 fullerenes and C60-containing composites cytotoxicity in vitro. Mater. Sci. Eng. C 2007, 27, 1121–1124.

    Article  Google Scholar 

  13. Johnston, H. J.; Hutchinson, G. R.; Christensen, F. M.; Aschberger, K.; Stone, V. The biological mechanisms and physicochemical characteristics responsible for driving fullerene toxicity. Toxicol. Sci. 2010, 114, 162–182.

    Article  Google Scholar 

  14. Prylutska, S.; Bilyy, R.; Overchuk, M.; Bychko, A.; Andreichenko, K.; Stoika, R.; Rybalchenko, V.; Prylutskyy, Y.; Tsierkezos, N. G.; Ritter, U. Water-soluble pristine fullerenes C60 increase the specific conductivity and capacity of lipid model membrane and form the channels in cellular plasma membrane. J. Biomed. Nanotechnol. 2012, 8, 522–527.

    Article  Google Scholar 

  15. Bedrov, D.; Smith, G. D.; Davande, H.; Li, L. W. Passive transport of C60 fullerenes through a lipid membrane: A molecular dynamics simulation study. J. Phys. Chem. B 2008, 112, 2078–2084.

    Article  Google Scholar 

  16. Qiao, R.; Roberts, A. P.; Mount, A. S.; Klaine, S. J.; Ke, P. C. Translocation of C60 and its derivatives across a lipid bilayer. Nano Lett. 2007, 7, 614–619.

    Article  Google Scholar 

  17. Gharbi, N.; Pressac, M.; Hadchouel, M.; Szwarc, H.; Wilson, S. R.; Moussa, F. [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005, 5, 2578–2585.

    Article  Google Scholar 

  18. Prylutska, S. V.; Grynyuk, I. I.; Matyshevska, O. P.; Prylutskyy, Y. I.; Ritter, U.; Scharff, P. Anti-oxidant properties of C60 fullerenes in vitro. Fullerenes, Nanotubes, Carbon Nanostruct. 2008, 16, 698–705.

    Article  Google Scholar 

  19. Prylutska, S. V.; Burlaka, A. P.; Klymenko, P. P.; Grynyuk, I. I.; Prylutskyy, Y. I.; Schü tze, C.; Ritter, U. Using water-soluble C60 fullerenes in anticancer therapy. Cancer Nanotechnol. 2011, 2, 105–110.

    Article  Google Scholar 

  20. Prylutska, S. V.; Burlaka, A. P.; Prylutskyy, Y. I.; Ritter, U.; Scharff, P. Pristine C(60) fullerenes inhibit the rate of tumor growth and metastasis. Exp. Oncol. 2011, 33, 162–164.

    Google Scholar 

  21. Chen, Z. Y.; Ma, L. J.; Liu, Y.; Chen, C. Y. Applications of functionalized fullerenes in tumor theranostics. Theranostics 2012, 2, 238–250.

    Article  Google Scholar 

  22. Didenko, G.; Prylutska, S.; Kichmarenko, Y.; Potebnya, G.; Prylutskyy, Y.; Slobodyanik, N.; Ritter, U.; Scharff, P. Evaluation of the antitumor immune response to C60 fullerene. Materialwiss. Werkstofftech. 2013, 44, 124–128.

    Article  Google Scholar 

  23. Kato, S.; Aoshima, H.; Saitoh, Y.; Miwa, N. Fullerene-C60 derivatives prevent UV-irradiation/TiO2-induced cytotoxicity on keratinocytes and 3D-skin tissues through antioxidant actions. J. Nanosci. Nanotechnol. 2014, 14, 3285–3291.

    Article  Google Scholar 

  24. Bozdaganyan, M. E.; Orekhov, P. S.; Shaytan, A. K.; Shaitan, K. V. Comparative computational study of interaction of C60-fullerene and tris-malonyl-C60-fullerene isomers with lipid bilayer: Relation to their antioxidant effect. PLoS One 2014, 9, e102487.

    Article  Google Scholar 

  25. Zhu, J. D.; Ji, Z. Q.; Wang, J.; Sun, R. H.; Zhang, X.; Gao, Y.; Sun, H. F.; Liu, Y. F.; Wang, Z.; Li, A. D. et al. Tumorinhibitory effect and immunomodulatory activity of fullerol C60(OH)x. Small 2008, 4, 1168–1175.

    Article  Google Scholar 

  26. Evstigneev, M. P.; Buchelnikov, A. S.; Voronin, D. P.; Rubin, Y. V.; Belous, L. F.; Prylutskyy, Y. I.; Ritter, U. Complexation of C60 fullerene with aromatic drugs. ChemPhysChem 2013, 14, 568–578.

    Article  Google Scholar 

  27. Prylutskyy, Y. I.; Evstigneev, M. P.; Pashkova, I. S.; Wyrzykowski, D.; Woziwodzka, A.; Golunski, G.; Piosik, J.; Cherepanov, V. V.; Ritter, U. Characterization of C60 fullerene complexation with antibiotic doxorubicin. Phys. Chem. Chem. Phys. 2014, 16, 23164–23172.

    Article  Google Scholar 

  28. Prylutska, S. V.; Didenko, G. V.; Potebnya, G. P.; Bogutska, K. I.; Prylutskyy, Y. I.; Ritter, U.; Scharff, P. Toxic effect of C60 fullerene-doxorubicin complex towards tumor and normal cells in vitro. Biopolym. Cell 2014, 30, 372–376.

    Article  Google Scholar 

  29. Panchuk, R. R.; Prylutska, S. V.; Chumak, V. V.; Skorokhyd, N. R.; Lehka, L. V.; Evstigneev, M. P.; Prylutskyy, Y. I.; Berger, W.; Heffter, P.; Scharff, P. et al. Application of C60 fullerene-doxorubicin complex for tumor cell treatment in vitro and in vivo. J. Biomed. Nanotechnol. 2015, 11, 1139–1152.

    Article  Google Scholar 

  30. Prylutska, S. V.; Skivka, L. M.; Didenko, G. V.; Prylutskyy, Y. I.; Evstigneev, M. P.; Potebnya, G. P.; Panchuk, R. R.; Stoika, R. S.; Ritter, U.; Scharff, P. Complex of C60 fullerene with doxorubicin as a promising agent in antitumor therapy. Nanoscale Res. Lett. 2015, 10, 499.

    Article  Google Scholar 

  31. Prylutskyy, Y. I.; Evstigneev, M. P.; Cherepanov, V. V.; Kyzyma, O. A.; Bulavin, L. A.; Davidenko, N. A.; Scharff, P. Structural organization of C60 fullerene, doxorubicin, and their complex in physiological solution as promising antitumor agents. J. Nanopart. Res. 2015, 17, 45.

    Article  Google Scholar 

  32. Prylutskyy, Y. I.; Cherepanov, V. V.; Evstigneev, M. P.; Kyzyma, O. A.; Petrenko, V. I.; Styopkin, V. I.; Bulavin, L. A.; Davidenko, N. A.; Wyrzykowski, D.; Woziwodzka, A. et al. Structural self-organization of C60 and cisplatin in physiological solution. Phys. Chem. Chem. Phys. 2015, 17, 26084–26092.

    Article  Google Scholar 

  33. Levi, J. A.; Aroney, R. S.; Dalley, D. N. Haemolytic anaemia after cisplatin treatment. BMJ 1981, 282, 2003–2004.

    Article  Google Scholar 

  34. Aguilar-Markulis, N. V.; Beckley, S.; Priore, R.; Mettlin, C. Auditory toxicity effects of long-term cisdichlorodiammineplatinum II therapy in genitourinary cancer patients. J. Surg. Oncol. 1981, 16, 111–123.

    Article  Google Scholar 

  35. Zhou, W. J.; Kavelaars, A.; Heijnen, C. J. Metformin prevents cisplatin-induced cognitive impairment and brain damage in mice. PLoS One 2016, 11, e0151890.

    Google Scholar 

  36. Perobelli, J. E. Effects of anticancer drugs in reproductive parameters of juvenile male animals and role of protective agents. Anticancer Agents Med. Chem., in press, DOI: 10.2174/1871520616666160219162033.

  37. Glatter, O. A new method for the evaluation of small-angle scattering data. J. Appl. Crystallogr. 1977, 10, 415–421.

    Article  Google Scholar 

  38. Glatter, O. The interpretation of real-space information from small-angle scattering experiments. J. Appl. Crystallogr. 1979, 12, 166–175.

    Article  Google Scholar 

  39. Gao, J.; Wang, T.; Qiu, S.; Zhu, Y.; Liang, L.; Zheng, Y. Structure-based drug design of small molecule peptide deformylase inhibitors to treat cancer. Molecules 2016, 21, 396.

    Article  Google Scholar 

  40. Fukunishi, Y.; Mashimo, T.; Misoo, K.; Wakabayashi, Y.; Miyaki, T.; Ohta, S.; Nakamura, M.; Ikeda, K. Miscellaneous topics in computer-aided drug design: Synthetic accessibility and GPU computing, and other topics. Curr. Pharm. Des. 2016, 22, 3555–3568.

    Article  Google Scholar 

  41. Pandey, R. K.; Kumbhar, B. V.; Sundar, S.; Kunwar, A.; Prajapati, V. K. Structure-based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogs as potential inhibitor against Leishmania donovani trypanothione reductase. J. Recept. Signal Transduct. Res., in press, DOI: 10.3109/10799893.2016.1171344.

  42. Andreichenko, K. S.; Prylutska, S. V.; Medynska, K. O.; Bogutska, K. I.; Nurishchenko, N. E.; Prylutskyy, Y. I.; Ritter, U.; Scharff, P. Effect of fullerene C60 on ATPase activity and superprecipitation of skeletal muscle actomyosin. Ukr. Biochim. Zh. 2013, 85, 20–26.

    Article  Google Scholar 

  43. Xu, X.; Li, R. B.; Ma, M.; Wang, X.; Wang, Y. H.; Zou, H. F. Multidrug resistance protein P-glycoprotein does not recognize nanoparticle C60: Experiment and modeling. Soft Matter 2012, 8, 2915–2923.

    Article  Google Scholar 

  44. Liu, X. Y.; Liu, S. P.; Jiang, J.; Zhang, X.; Zhang, T. Inhibition of the JNK signaling pathway increases sensitivity of hepatocellular carcinoma cells to cisplatin by downregulating expression of P-glycoprotein. Eur. Rev. Med. Pharmacol. Sci. 2016, 20, 1098–1108.

    Google Scholar 

  45. Pastan, I.; Gottesman, M. M.; Ueda, K.; Lovelace, E.; Rutherford, A. V.; Willingham, M. C. A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc. Natl. Acad. Sci. USA 1988, 85, 4486–4490.

    Article  Google Scholar 

  46. Leslie, E. M.; Deeley, R. G.; Cole, S. P. C. Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol. Appl. Pharmacol. 2005, 204, 216–237.

    Article  Google Scholar 

  47. Sreenivasan, S.; Ravichandran, S.; Vetrivel, U.; Krishnakumar, S. In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells. Bioinformation 2012, 8, 13–19.

    Article  Google Scholar 

  48. Li, Q. C.; Liang, Y.; Hu, G. R.; Tian, Y. Enhanced therapeutic efficacy and amelioration of cisplatin-induced nephrotoxicity by quercetin in 1,2-dimethyl hydrazine-induced colon cancer in rats. Indian J. Pharmacol. 2016, 48, 168–171.

    Article  Google Scholar 

  49. Kovach, J. S.; Moertel, C. G.; Schutt, A. J.; Reitemeier, R. G.; Hahn, R. G. Phase II study of cis-diamminedichloroplatinum (NSC-119875) in advanced carcinoma of the large bowel. Cancer Chemother. Rep. 1973, 57, 357–359.

    Google Scholar 

  50. Friedlander, M.; Kaye, S. B.; Sullivan, A.; Atkinson, K.; Elliott, P.; Coppleson, M.; Houghton, R.; Solomon, J.; Green, D.; Russell, P. et al. Cervical-carcinoma: A drug-responsive tumor—experience with combined cisplatin, vinblastine, and bleomycin therapy. Gynecol. Oncol. 1983, 16, 275–281.

    Article  Google Scholar 

  51. Prestayko, A. W.; D’Aoust, J. C.; Issell, B. F.; Crooke, S. T. Cisplatin (cis-diamminedichloroplatinum II). Cancer Treat. Rev. 1979, 6, 17–39.

    Article  Google Scholar 

  52. Hashmi, H.; Maqbool, A.; Ahmed, S.; Ahmed, A.; Sheikh, K.; Ahmed, A. Concurrent cisplatin-based chemoradiation in squamous cell carcinoma of cervix. J. Coll. Physicians Surg. Pak. 2016, 26, 302–305.

    Google Scholar 

  53. Jendželovská, Z.; Jendželovský, R.; Hilovská, L.; Koval, J.; Mikeš, J.; Fedorocko, P. Single pre-treatment with hypericin, a St. John’s wort secondary metabolite, attenuates cisplatin-and mitoxantrone-induced cell death in A2780, A2780cis and HL-60 cells. Toxicol. in Vitro 2014, 28, 1259–1273.

    Article  Google Scholar 

  54. Xu, H.-W.; Xu, L.; Hao, J.-H.; Qin, C.-Y.; Liu, H. Expression of P-glycoprotein and multidrug resistanceassociated protein is associated with multidrug resistance in gastric cancer. J. Int. Med. Res. 2010, 38, 34–42.

    Article  Google Scholar 

  55. Lin, X. J.; Howell, S. B. DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol. Cancer Ther. 2006, 5, 1239–1247.

    Article  Google Scholar 

  56. Sui, X.; Luo, C.; Wang, C.; Zhang, F. W.; Zhang, J. Y.; Guo, S. W. Graphene quantum dots enhance anticancer activity of cisplatin via increasing its cellular and nuclear uptake. Nanomedicine 2016, 12, 1997–2006.

    Google Scholar 

  57. He, G. D.; He, G. L.; Zhou, R. Y.; Pi, Z. B.; Zhu, T. Q.; Jiang, L. M.; Xie, Y. B. Enhancement of cisplatin induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo. Biochem. Biophys. Res. Commun. 2016, 469, 1075–1082.

    Article  Google Scholar 

  58. Desbois, N.; Pertuit, D.; Moretto, J.; Cachia, C.; Chauffert, B.; Bouyer, F. cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]_naphthyridin-6-ones: Synthesis and cytotoxicity in human cancer cell lines in vitro. Eur. J. Med. Chem. 2013, 69, 719–727.

    Article  Google Scholar 

  59. Lee, Y.; Kim, Y. J.; Choi, Y. J.; Lee, J. W.; Lee, S.; Chung, H. W. Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells. Food Chem. Toxicol. 2012, 50, 2397–2406.

    Article  Google Scholar 

  60. Roy, M.; Mukherjee, S. Reversal of resistance towards cisplatin by curcumin in cervical cancer cells. Asian Pac. J. Cancer Prev. 2014, 15, 1403–1410.

    Article  Google Scholar 

  61. Neumann, W.; Crews, B. C.; Sárosi, M. B.; Daniel, C. M.; Ghebreselasie, K.; Scholz, M. S.; Marnett, L. J.; Hey-Hawkins, E. Conjugation of cisplatin analogues and cyclooxygenase inhibitors to overcome cisplatin resistance. ChemMedChem 2015, 10, 183–192.

    Article  Google Scholar 

  62. Wang, T. H.; Wan, J. Y.; Gong, X.; Li, H. Z.; Cheng, Y. Tetrandrine enhances cytotoxicity of cisplatin in human drugresistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1. Oncol. Rep. 2012, 28, 1681–1686.

    Google Scholar 

  63. Pariente, R.; Pariente, J. A.; Rodríguez, A. B.; Espino, J. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin-induced cytotoxicity and apoptosis: Effects on oxidative stress and DNA fragmentation. J. Pineal Res. 2016, 60, 55–64.

    Article  Google Scholar 

  64. Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kepp, O.; Castedo, M.; Kroemer, G. Molecular mechanisms of cisplatin resistance. Oncogene 2012, 31, 1869–1883.

    Article  Google Scholar 

  65. Ormerod, M. G.; O’Neill, C. F.; Robertson, D.; Harrap, K. R. Cisplatin induces apoptosis in a human ovarian carcinoma cell line without concomitant internucleosomal degradation of DNA. Exp. Cell Res. 1994, 211, 231–237.

    Article  Google Scholar 

  66. Ma, S. H.; Tan, W. H.; Du, B. T.; Liu, W.; Li, W. J.; Che, D. H.; Zhang, G. M. Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression. Mol. Med. Rep. 2016, 13, 3342–3348.

    Google Scholar 

  67. Golunski, G.; Woziwodzka, A.; Iermak, I.; Rychlowski, M.; Piosik, J. Modulation of acridine mutagen ICR191 intercalation to DNA by methylxanthines-analysis with mathematical models. Bioorg. Med. Chem. 2013, 21, 3280–3289.

    Article  Google Scholar 

  68. Woziwodzka, A.; Gwizdek-Wisniewska, A.; Piosik, J. Caffeine, pentoxifylline and theophylline form stacking complexes with IQ-type heterocyclic aromatic amines. Bioorg. Chem. 2011, 39, 10–17.

    Article  Google Scholar 

  69. Woziwodzka, A.; Golunski, G.; Wyrzykowski, D.; Kazmierkiewicz, R.; Piosik, J. Caffeine and other methylxanthines as interceptors of food-borne aromatic mutagens: Inhibition of Trp-P-1 and Trp-P-2 mutagenic activity. Chem. Res. Toxicol. 2013, 26, 1660–1673.

    Article  Google Scholar 

  70. Golunski, G.; Borowik, A.; Derewonko, N.; Kawiak, A.; Rychlowski, M.; Woziwodzka, A.; Piosik, J. Pentoxifylline as a modulator of anticancer drug doxorubicin. Part II: Reduction of doxorubicin DNA binding and alleviation of its biological effects. Biochimie 2016, 123, 95–102.

    Google Scholar 

  71. Golunski, G.; Borowik, A.; Lipinska, A.; Romanik, M.; Derewonko, N.; Woziwodzka, A.; Piosik, J. Pentoxifylline affects idarubicin binding to DNA. Bioorg. Chem. 2016, 65, 118–125.

    Article  Google Scholar 

  72. Orel, V.; Shevchenko, A.; Romanov, A.; Tselepi, M.; Mitrelias, T.; Barnes, C. H. W.; Burlaka, A.; Lukin, S.; Shchepotin, I. Magnetic properties and antitumor effect of nanocomplexes of iron oxide and doxorubicin. Nanomedicine 2015, 11, 47–55.

    Google Scholar 

  73. Prylutska, S. V.; Korolovych, V. F.; Prylutskyy, Y. I.; Evstigneev, M. P.; Ritter, U.; Scharff, P. Tumor-inhibitory effect of C60 fullerene complex with doxorubicin. Nanomed. Nanobiol. 2015, 2, 49–53.

    Google Scholar 

  74. Liu, X. X.; Liu, Y.; Hao, J. J.; Zhao, X. L.; Lang, Y. Z.; Fan, F.; Cai, C.; Li, G. Y.; Zhang, L. J.; Yu, G. L. In vivo anti-cancer mechanism of low-molecular-weight fucosylated chondroitin sulfate (LFCS) from sea cucumber Cucumaria frondosa. Molecules 2016, 21, 625.

    Article  Google Scholar 

  75. Xu, Y. Z.; Li, Y. H.; Lu, W. J.; Lu, K.; Wang, C. T.; Li, Y.; Lin, H. J.; Kan, L. X.; Yang, S. Y.; Wang, S. Y. et al. YL4073 is a potent autophagy-stimulating antitumor agent in an in vivo model of Lewis lung carcinoma. Oncol. Rep. 2016, 35, 2081–2088.

    Google Scholar 

  76. Peng, X. C.; Chen, X. X.; Zhang, Y.; Wang, H. J.; Feng, Y. A novel inhibitor of Rho GDP-dissociation inhibitor a improves the therapeutic efficacy of paclitaxel in Lewis lung carcinoma. Biomed. Rep. 2015, 3, 473–477.

    Google Scholar 

  77. Fan, S. J.; Xu, Y.; Li, X.; Tie, L.; Pan, Y.; Li, X. J. Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: In silico, in vitro and in vivo studies. Biochim. Biophys. Acta 2014, 1842, 1742–1754.

    Article  Google Scholar 

  78. Niu, P. G.; Zhang, Y. X.; Shi, D. H.; Liu, Y.; Chen, Y. Y.; Deng, J. Cardamonin inhibits metastasis of Lewis lung carcinoma cells by decreasing mTOR activity. PLoS One 2015, 10, e0127778.

    Google Scholar 

  79. Liu, Y. Z.; Yang, C. M.; Chen, J. Y.; Liao, J. W.; Hu, M. L. Alpha-carotene inhibits metastasis in Lewis lung carcinoma in vitro, and suppresses lung metastasis and tumor growth in combination with taxol in tumor xenografted C57BL/6 mice. J. Nutr. Biochem. 2015, 26, 607–615.

    Article  Google Scholar 

  80. Das, S. K.; Eder, S.; Schauer, S.; Diwoky, C.; Temmel, H.; Guertl, B.; Gorkiewicz, G.; Tamilarasan, K. P.; Kumari, P.; Trauner, M. et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 2011, 333, 233–238.

    Article  Google Scholar 

  81. Tsoli, M.; Robertson, G. Cancer cachexia: Malignant inflammation, tumorkines, and metabolic mayhem. Trends Endocrinol. Metab. 2013, 24, 174–183.

    Article  Google Scholar 

  82. Porporato, P. E. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis 2016, 5, e200.

    Article  Google Scholar 

  83. Perego, P.; Righetti, S. C.; Supino, R.; Delia, D.; Caserini, C.; Carenini, N.; Bedogné, B.; Broome, E.; Krajewski, S.; Reed, J. C. et al. Role of apoptosis and apoptosis-related proteins in the cisplatin-resistant phenotype of human tumor cell lines. Apoptosis 1997, 2, 540–548.

    Article  Google Scholar 

  84. Jinushi, M. Immune regulation of therapy-resistant niches: Emerging targets for improving anticancer drug responses. Cancer Metastasis Rev. 2014, 33, 737–745.

    Article  Google Scholar 

  85. D’Arena, G.; Deaglio, S.; Laurenti, L.; de Martino, L.; de Feo, V.; Fusco, B. M.; Carella, A. M.; Cascavilla, N.; Musto, P. Targeting regulatory T cells for anticancer therapy. Mini Rev. Med. Chem. 2011, 11, 480–485.

    Article  Google Scholar 

  86. Shurin, M. R.; Naiditch, H.; Gutkin, D. W.; Umansky, V.; Shurin, G. V. ChemoImmunoModulation: Immune regulation by the antineoplastic chemotherapeutic agents. Curr. Med. Chem. 2012, 19, 1792–1803.

    Article  Google Scholar 

  87. Skivka, L. M.; Fedorchuk, O. G.; Bezdeneznykh, N. O.; Lykhova, O. O.; Semesiuk, N. I.; Kudryavets, Y. I.; Malanchuk, O. M. The effect of antineoplastic drug NSC63150 on immunogenicity of B16 melanoma. J. Exp. Integr. Med. 2014, 4, 93–105.

    Article  Google Scholar 

  88. Fedorchuk, O. G.; Pyaskovskaya, O. M.; Skivka, L. M.; Gorbik, G. V.; Trompak, O. O.; Solyanik, G. I. Paraneoplastic syndrome in mice bearing high-angiogenic variant of Lewis lung carcinoma: Relations with tumor derived VEGF. Cytokine 2012, 57, 81–88.

    Article  Google Scholar 

  89. Yang, X. L.; Ebrahimi, A.; Li, J.; Cui, Q. J. Fullerenebiomolecule conjugates and their biomedicinal applications. Int. J. Nanomedicine 2014, 9, 77–92.

    Article  Google Scholar 

  90. Turabekova, M.; Rasulev, B.; Theodore, M.; Jackman, J.; Leszczynska, D.; Leszczynski, J. Immunotoxicity of nanoparticles: A computational study suggests that CNTs and C60 fullerenes might be recognized as pathogens by Toll-like receptors. Nanoscale 2014, 6, 3488–3495.

    Article  Google Scholar 

  91. Prylutska, S. V.; Grynyuk, I. I.; Grebinyk, S. M.; Matyshevska, O. P.; Prylutskyy, Y. I.; Ritter, U.; Siegmund, C.; Scharff, P. Comperative study of biological action of fullerenes C60 and carbon nanotubes in thymus cells. Materialwiss. Werkstofftech. 2009, 40, 238–241.

    Article  Google Scholar 

  92. Prylutskyy, Y. I.; Petrenko, V. I.; Ivankov, O. I.; Kyzyma, O. A.; Bulavin, L. A.; Litsis, O. O.; Evstigneev, M. P.; Cherepanov, V. V.; Naumovets, A. G.; Ritter, U. On the origin of C60 fullerene solubility in aqueous solution. Langmuir 2014, 30, 3967–3970.

    Article  Google Scholar 

  93. Ritter, U.; Prylutskyy, Y. I.; Evstigneev, M. P.; Davidenko, N. A.; Cherepanov, V. V.; Senenko, A. I.; Marchenko, O. A.; Naumovets, A. G. Structural features of highly stable reproducible C60 fullerene aqueous colloid solution probed by various techniques. Fullerenes, Nanotubes, Carbon Nanostruct. 2015, 23, 530–534.

    Article  Google Scholar 

  94. Blanton, T. N.; Barnes, C. L.; Lelental, M. Preparation of silver behenate coatings to provide low-to mid-angle diffraction calibration. J. Appl. Cryst. 2000, 33, 172–173.

    Article  Google Scholar 

  95. Franke, D.; Kikhney, A. G.; Svergun, D. I. Automated acquisition and analysis of small angle X-ray scattering data. Nucl. Inst. Meth. Phys. Res. Sect. A 2012, 689, 52–59.

    Article  Google Scholar 

  96. Svergun, D. I. Determination of the regularization parameter in indirect-transform methods using perceptual criteria. J. Appl. Cryst. 1992, 25, 495–503.

    Article  Google Scholar 

  97. Li, J. Z.; Jaimes, K. F.; Aller, S. G. Refined structures of mouse P-glycoprotein. Protein Sci. 2014, 23, 34–46.

    Article  Google Scholar 

  98. Ramaen, O.; Leulliot, N.; Sizun, C.; Ulryck, N.; Pamlard, O.; Lallemand, J. Y.; van Tilbeurgh, H.; Jacquet, E. Structure of the human multidrug resistance protein 1 nucleotide binding domain 1 bound to Mg2+/ATP reveals a non-productive catalytic site. J. Mol. Biol. 2006, 359, 940–949.

    Article  Google Scholar 

  99. Vedadi, M.; Lew, J.; Artz, J.; Amani, M.; Zhao, Y.; Dong, A. P.; Wasney, G. A.; Gao, M.; Hills, T.; Brokx, S. et al. Genome-scale protein expression ans structural biology of Plasmodium falciparum and related Apicomplexan organisms. Mol. Biochem. Parasit. 2007, 151, 100–110.

    Article  Google Scholar 

  100. Warren, G. L.; Andrews, C. W.; Capelli, A. M.; Clarke, B.; LaLonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S. et al. A critical assessment of docking programs and scoring functions. J. Med. Chem. 2006, 49, 5912–5931.

    Article  Google Scholar 

  101. McMartin, C.; Bohacek, R. S. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput. Aided Mol. Des. 1997, 11, 333–344.

    Article  Google Scholar 

  102. Walker, P. R.; Kwast-Welfeld, J.; Gourdeau, H.; Leblanc, J.; Neugebauer, W.; Sikorska, M. Relationship between apoptosis and the cell cycle in lymphocytes: Roles of protein kinase C, tyrosine phosphorylation, and AP1. Exp. Cell Res. 1993, 207, 142–151.

    Article  Google Scholar 

  103. Mortelmans, K.; Zeiger, E. The Ames Salmonella/microsome mutagenicity assay. Mutat. Res. 2000, 455, 29–60.

    Article  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the technical support from Clement Blanchet (EMBL) at the P12 BioSAXS beamline (EMBL/DESY, PETRA III). The research was partially supported by Russian Science Fund (No. 14-14-00328). S. Prylutska receives financial support by the Academician Platon Kostyuk Foundation, R. Panchuk receives financial support by West-Ukrainian BioMedical Research Center (WUMBRC) and by grant of Nationl Academy of Sciences of Ukraine for young scientists.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yuriy Prylutskyy, Jacek Piosik or Maxim Evstigneev.

Additional information

These authors contributed equally to this work.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Prylutska, S., Panchuk, R., Gołuński, G. et al. C60 fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance. Nano Res. 10, 652–671 (2017). https://doi.org/10.1007/s12274-016-1324-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-016-1324-2

Keywords

  • molecular docking
  • small-angle X-ray scattering
  • apoptosis
  • mutagenic activity
  • Lewis lung carcinoma (LLC)
  • cytotoxicity