Multiple mechanisms underlying the anticancer action of nanocrystalline fullerene

• Published in: European journal of pharmacology 2007-07, Vol.568 (1), p.89-98
• Main Authors: Harhaji, Ljubica, Isakovic, Aleksandra, Raicevic, Nevena, Markovic, Zoran, Todorovic-Markovic, Biljana, Nikolic, Nadezda, Vranjes-Djuric, Sanja, Markovic, Ivanka, Trajkovic, Vladimir
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Autophagy; Biological and medical sciences; C 60 fullerene; Cell Cycle - drug effects; Cell Death - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Fullerenes - pharmacology; Glial Fibrillary Acidic Protein - metabolism; Glioma - drug therapy; Glioma - metabolism; Humans; Lipid Peroxidation - drug effects; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Mitogen-activated proteine kinases; Nanoparticles; Necrosis; Oxidative stress; Pharmacology. Drug treatments; Rats; Reactive Oxygen Species - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.04.041

Using the rat glioma cell line C6 and the human glioma cell line U251, we demonstrate the multiple mechanisms underlying the in vitro anticancer effects of the C 60 fullerene water suspension (nano-C 60 or nC 60) produced by solvent exchange method. Nano-C 60 in a dose-dependent manner reduced the tumor cell numbers after 24 h of incubation. The observed antiglioma action of nC 60 at high concentration (1 μg/ml) was due to a reactive oxygen species-mediated necrotic cell damage that was partly dependent on oxidative stress-induced activation of extracellular signal-regulated kinase (ERK). On the other hand, low-dose nC 60 (0.25 μg/ml) did not induce either necrotic or apoptotic cell death, but caused oxidative stress/ERK-independent cell cycle block in G 2/M phase and subsequent inhibition of tumor cell proliferation. Treatment with either high-dose or low-dose nC 60 caused the appearance of acidified intracytoplasmic vesicles indicative of autophagy, but only the antiglioma effect of low-dose nC 60 was significantly attenuated by inhibiting autophagy with bafilomycin A1. Importantly, primary rat astrocytes were less sensitive than their transformed counterparts to a cytostatic action of low-dose nC 60. These data provide grounds for further development of nC 60 as an anticancer agent.