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

Svitlana Prylutska , Rostyslav Panchuk , Grzegorz Gołuński , Larysa Skivka , Yuriy Prylutskyy , Vasyl Hurmach , Nadya Skorohyd , Agnieszka Borowik , Anna Woziwodzka , Jacek Piosik , Olena Kyzyma , Vasil Garamus , Leonid Bulavin , Maxim Evstigneev , Anatoly Buchelnikov , Rostyslav Stoika , Walter Berger , Uwe Ritter , Peter Scharff

Abstract

We formulated and analyzed a novel nanoformulation of the anticancer drug cisplatin (Cis) with C 60 fullerene (C 60 +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 C 60 +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 C 60 +Cis complex increases tumor growth inhibition, when compared to Cis or C 60 fullerenes alone. Simultaneously, we conducted a molecular docking study and performed an Ames test. Molecular docking specifies the capability of a C 60 fullerene to form van der Waals interactions with potential binding sites on P-glycoprotein (P-gp), multidrug resist ance 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 C 60 +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 o f secondary neoplasm formation. In conclusion, the C 60 +Cis complex effectively induced tumor cell death in vitro and inhibited tumor growth in vivo , overcoming drug resistance likely by the potential of the C 60 fullerene to interact with P-gp, MRP-1, and MRP-2 molecules. Thus, the C 60 +Cis complex might be a potential novel chemotherapy modification.
Author Svitlana Prylutska
Svitlana Prylutska,,
-
, Rostyslav Panchuk
Rostyslav Panchuk,,
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, Grzegorz Gołuński MWB UG i GUMed
Grzegorz Gołuński,,
- Intercollegiate Faculty of Biotechnology UG
, Larysa Skivka
Larysa Skivka,,
-
, Yuriy Prylutskyy
Yuriy Prylutskyy,,
-
, Vasyl Hurmach
Vasyl Hurmach,,
-
, Nadya Skorohyd
Nadya Skorohyd,,
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, Agnieszka Borowik MWB UG i GUMed
Agnieszka Borowik,,
- Intercollegiate Faculty of Biotechnology UG
, Anna Woziwodzka KBMiK
Anna Woziwodzka,,
- Department of Molecular and Cellular Biology
, Jacek Piosik KBMiK
Jacek Piosik,,
- Department of Molecular and Cellular Biology
et al.`
Journal seriesNano Research, ISSN 1998-0124
Issue year2017
Vol10
No2
Pages652-671
Publication size in sheets0.95
Keywords in Englishmolecular docking, small-angle X-ray scattering, apoptosis, mutagenic activity, Lewis lung carcinoma (LLC), cytotoxicity
DOIDOI:10.1007/s12274-016-1324-2
URL http://link.springer.com/content/pdf/10.1007%2Fs12274-016-1324-2.pdf
Languageen angielski
Score (nominal)45
ScoreMinisterial score = 45.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 45.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 7.354 (2) - 2016=7.679 (5)
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