TY - JOUR
T1 - Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets
AU - Zhou, Teng
AU - Zhang, Bo
AU - Wei, Peng
AU - Du, Yipeng
AU - Zhou, Hejiang
AU - Yu, Meifang
AU - Yan, Liang
AU - Zhang, Wendi
AU - Nie, Guangjun
AU - Chen, Chunying
AU - Tu, Yaping
AU - Wei, Taotao
N1 - Funding Information:
The authors thank Prof. Myron L. Toews (University of Nebraska Medical Center) for critical reading and editing of the manuscript. The authors are also indebted to Peng Xue, Junfeng Hao, Yanxia Jia (Institute of Biophysics, Chinese Academy of Sciences) and Lei Guo (Beijing Huawei Zhongyi Technology Co. Ltd.) for technical assistances. This work was supported by grants from the National Basic Research Program of China (Grants 2012CB934003 , 2010CB833701 and 2010CB933401 ), the National Natural Science Foundation of China (Grants 31100595 and 31300683 ), the Major Equipment Program of China (Grant 2011YQ030134 ), and the Nebraska State LB595 Research Program of USA.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration invitro and invivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in PEG-GO-exposed breast cancer versus non-cancerous cells. The results indicated that PEG-GO selectively down-regulated PGC-1α in breast cancer cells and thus modified the expression of diverse energy generation-related proteins, which accounts for the inhibition of OXPHOS. The inhibition of OXPHOS by PEG-GO significantly reduced ATP production and impaired assembly of the F-actin cytoskeleton in breast cancer cells, which is required for the migratory and invasive phenotype of cancer cells. Taken together, these effects of PEG-GO on cancer cell metastasis may allow the development of a new approach to treat metastatic breast cancer.
AB - Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration invitro and invivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in PEG-GO-exposed breast cancer versus non-cancerous cells. The results indicated that PEG-GO selectively down-regulated PGC-1α in breast cancer cells and thus modified the expression of diverse energy generation-related proteins, which accounts for the inhibition of OXPHOS. The inhibition of OXPHOS by PEG-GO significantly reduced ATP production and impaired assembly of the F-actin cytoskeleton in breast cancer cells, which is required for the migratory and invasive phenotype of cancer cells. Taken together, these effects of PEG-GO on cancer cell metastasis may allow the development of a new approach to treat metastatic breast cancer.
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U2 - 10.1016/j.biomaterials.2014.08.033
DO - 10.1016/j.biomaterials.2014.08.033
M3 - Article
C2 - 25212524
AN - SCOPUS:84907260833
VL - 35
SP - 9833
EP - 9843
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 37
ER -