C60 fullerene and its nanocomplexes with anticancer drugs modulate circulating phagocyte functions and dramatically increase ROS generation in transformed monocytes

Larysa M Skivka,Ievgeniia V Opeida,Uwe Ritter,Nataliia M Khranovska,Yuriy I Prylutskyy,Svitlana V Prylutska,Vasyl V Hurmach,Leonid F Sukhodub,Mariia P Rudyk

doi:10.1186/s12645-017-0034-0

Abstract

BackgroundC60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C60 fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro.MethodsAnalysis of the metabolic profile of phagocytes exposed to C60 fullerene in vitro revealed augmented phagocytic activity and down-regulated reactive nitrogen species generation in these cells. Additionally, cytofluorimetric analysis showed that C60 fullerene can exert direct cytotoxic effect on normal and transformed phagocytes through the vigorous induction of intracellular reactive oxygen species generation.ResultsCytotoxic action as well as the pro-oxidant effect of C60 fullerene was more pronounced toward malignant phagocytes. At the same time, C60 fullerenes have the ability to down-regulate the pro-oxidant effect of cisplatin on normal cells. These results indicate that C60 fullerenes may influence phagocyte metabolism and have both pro-oxidant and antioxidant properties.ConclusionsThe antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity.

Highlights

C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells
The antineoplastic effect of C60 fullerene has been observed by direct toxic effect on tumor cells, as well as through the modulation of the functions of effector cells of antitumor immunity
It was important to investigate the effect of C60 fullerenes and their nanocomplexes with anticancer drugs on different metabolic reactions of nonsensitized human peripheral blood phagocytes as well as myeloid leukemia cells U937, and revealed potential receptive membrane and intracellular structures, which could be involved in such effect

Summary

Introduction

C60 fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C60 fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. We have demonstrated that conjugation of Dox and Cisplatin (Cis) with the C 60 fullerene led to significant increase in its toxicity toward various human tumor cell lines in vitro and greatly enhances the inhibitory effect of these drugs on the growth of Lewis lung carcinoma in vivo (Prylutska et al 2015a, b, 2017 Panchuk et al 2015). It is well documented that the underlying mechanism of antineoplastic effect of C 60 fullerene-based nanoformulations is related with the combination of the direct effect on tumor cells (modulation of oxidative stress, apoptosis, necrosis, and autophagy), their effect on tumor microenvironment (reduction of the blood supply to tumor tissues), and activation of the host immune system (Dellinger et al 2013; Harhaji et al 2007; Shi and Li 2012)

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