title: The inhibition of migration and invasion of cancer cells by graphene via the impairment of mitochondrial respiration.
abstract: Graphene and its derivatives have become important nanomaterials worldwide and have potential medical applications including in vivo diagnosis, drug delivery, and photothermal therapy of cancer. However, little is known about their effect on the metastasis of cancer cells, which is the cause of over 90% of patient deaths. In the present investigation, we provide direct evidence that low concentrations of pristine graphene and graphene oxide show no apparent influence on the viability of MDA-MB-231 human breast cancer cells, PC3 human prostate cancer cells, as well as B16F10 mouse melanoma cells. However, both pristine graphene and graphene oxide can effectively inhibit the migration and invasion of these cancer cells. Further studies indicate that exposure of cells to graphene led to the direct inhibition of the electron transfer chain complexes I, II, III and IV, most likely by disrupting electron transfer between iron-sulfur centers, which is due to its stronger ability to accept electrons compared to iron-sulfur clusters through theoretical calculations. The decreased electron transfer chain activity caused a reduction in the production of ATP and subsequent impairment of F-actin cytoskeleton assembly, which is crucial for the migration and invasion of metastatic cancer cells. The inhibition of cancer cell metastasis by graphene and graphene oxide might provide new insights into specific cancer treatment.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hejiang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Yu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhou
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Jia
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. Electronic address: gaox@ihep.ac.cn.
authors.forename: Xingfa
authors.initials: X
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China. Electronic address: chenchy@nanoctr.cn.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: weitt@moon.ibp.ac.cn.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wei
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D006108:Graphite / Q000494:pharmacology*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011166:Porphyrins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
chemical_list: D007506:Iron-Sulfur Proteins; D011166:Porphyrins; D006108:Graphite; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase
keywords: Cancer cell; Electron transfer chain; Graphene; Iron-sulfur center; Metastasis; Mitochondria