PEG-GO@XN nanocomposite suppresses breast cancer metastasis via inhibition of mitochondrial oxidative phosphorylation and blockade of epithelial-to-mesenchymal transition

Jialing Zhang, Liang Yan, Peng Wei, Ruyi Zhou, Chaoju Hua, Min Xiao, Yaping Tu, Zhanjun Gu, Taotao Wei

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Metastatic breast cancer is a significant contributor to mortality among women, but its complex regulation represents a barrier to precision targeting. In the present study, a graphene-based nanocomposite which probes and selectively inhibits cancer cell motility is described. By controllable coupling of prenylated chalcone xanthohumol, an efficient inhibitor of mitochondrial electron transport chain complex I, with PEGylated graphene oxide nanosheet, a PEG-GO@XN nanocomposite with good stability and biocompatibility is synthesized. PEG-GO@XN is capable of inhibiting mitochondrial oxidative phosphorylation selectively in MDA-MB-231 and MDA-MB-436 metastatic breast cancer cells. PEG-GO@XN reduces the production of ATP, impairs the formation of F-actin cytoskeleton in the lamellipodia, and blocks the migration and invasion of breast cancer cells in vitro, without interfering the proliferation and metabolism of non-cancerous cells. More importantly, PEG-GO@XN suppresses the metastasis of MDA-MB-231 cells to lung in nude mice. PEG-GO@XN abolishes the TGF-β1-induced down-regulation of E-cadherin and up-regulation of N-cadherin, vimentin, Snail and Twist, thus causes the maintenance of “epithelial-like” rather than the “mesenchymal-like” features, and decreases the motility potential of breast cancer cells. Taken together, this research unveils the enormous potential of PEG-GO@XN to suppress metastatic breast cancer by selective targeting oxidative phosphorylation and epithelial-mesenchymal transition of cancer cells and thereby providing insights on metastatic cancer treatment.

Original languageEnglish (US)
Article number173866
JournalEuropean Journal of Pharmacology
Volume895
DOIs
StatePublished - Mar 15 2021

All Science Journal Classification (ASJC) codes

  • Pharmacology

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