Graphene Enhances Cellular Proliferation through Activating the Epidermal Growth Factor Receptor.
Graphene has promising applications in food packaging, water purification, and detective sensors for contamination monitoring. However, the biological effects of graphene are not fully understood. It is necessary to clarify the potential risks of graphene exposure to humans through diverse routes, such as foods. In the present study, graphene, as the model nanomaterial, was used to test its potential effects on the cell proliferation based on multiple representative cell lines, including HepG2, A549, MCF-7, and HeLa cells. Graphene was characterized by Raman spectroscopy, particle size analysis, atomic force microscopy, and transmission electron microscopy. The cellular responses to graphene exposure were evaluated using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and alamarBlue assays. Rat cerebral astrocyte cultures, as the non-cancer cells, were used to assess the potential cytotoxicity of graphene as well. The results showed that graphene stimulation enhanced cell proliferation in all tested cell cultures and the highest elevation in cell growth was up to 60%. A western blot assay showed that the expression of epidermal growth factor (EGF) was upregulated upon graphene treatment. The phosphorylation of EGF receptor (EGFR) and the downstream proteins, ShC and extracellular regulating kinase (ERK), were remarkably induced, indicating that the activation of the mitogen-activated protein kinase (MAPK)/ERK signaling pathway was triggered. The activation of PI3 kinase p85 and AKT showed that the PI3K/AKT signaling pathway was also involved in graphene-induced cell proliferation, causing the increase of cell ratios in the G2/M phase. No influences on cell apoptosis were observed in graphene-treated cells when compared to the negative controls, proving the low cytotoxicity of this emerging nanomaterial. The findings in this study revealed the potential cellular biological effect of graphene, which may give useful hints on its biosafety evaluation and the further exploration of the bioapplication.
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Wei
W
Liu
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, People's Republic of China.
Cheng
C
Sun
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, People's Republic of China.
Chunyang
C
Liao
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, People's Republic of China.
Lin
L
Cui
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Haishan
H
Li
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, People's Republic of China.
Guangbo
G
Qu
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Wenlian
W
Yu
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Naining
N
Song
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Yuan
Y
Cui
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Zheng
Z
Wang
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Wenping
W
Xie
Institute of Chemical Safety, Chinese Academy of Inspection and Quarantine , Beijing 100124, People's Republic of China.
Huiming
H
Chen
Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085, People's Republic of China.
Qunfang
Q
Zhou
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D004815:Epidermal Growth Factor; D006108:Graphite; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
EGFR; biosafety; cell proliferation; cytotoxicity; graphene