C_{ass="a-plus-plus">60} fullerene enhances cisplatin anticancer activity and overcomes tumor cell drug resistance

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• 作者：Svitlana Prylutska ; Rostyslav Panchuk ; Grzegorz Gołuński ; Larysa Skivka…
• 关键词：molecular docking ; small ; angle X ; ray scattering ; apoptosis ; mutagenic activity ; Lewis lung carcinoma (LLC) ; cytotoxicity
• 刊名：Nano Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：10
• 期：2
• 页码：652-671
• 全文大小：
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Nanotechnology; Materials Science, general; Atomic/Molecular Structure and Spectra; Condensed Matter Physics; Biotechnology; Biomedicine, general;
• 出版者：Tsinghua University Press
• ISSN：1998-0000
• 卷排序：10

文摘

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.