期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 568, 期 1-3, 页码 89-98出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2007.04.041
关键词
C-60 fullerene; necrosis; autophagy; oxidative stress; mitogen-activated proteine kinases
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 mu g/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 mu g/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. (C) 2007 Elsevier B.V. All rights reserved.
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