Autophagy-mediated chemosensitization in cancer cells by fullerene C60 nanocrystal

Autophagy. 2009 Nov;5(8):1107-17. doi: 10.4161/auto.5.8.9842. Epub 2009 Nov 19.

Abstract

Autophagy may represent a common cellular response to nanomaterials, and modulation of autophagy holds great promise for improving the efficacy of cancer therapy. Fullerene C60 possesses potent anti-cancer activities, but its considerable toxicity towards normal cells may hinder its practical applications. It has been reported that fullerene C60 induces certain hallmarks of autophagy in cancer cells. Here we show that the water-dispersed nanocrystal of underivatized fullerene C60 (Nano-C60) at noncytotoxic concentrations caused authentic autophagy and sensitized chemotherapeutic killing of both normal and drug-resistant cancer cells in a reactive oxygen species (ROS)-dependent and photo-enhanced fashion. We further demonstrated that the chemosensitization effect of Nano-C60 was autophagy-mediated and required a functional Atg5, a key gene in the autophagy signaling pathway. Our results revealed a novel biological function for Nano-C60 in enhancing the cytotoxic action of chemotherapeutic agents through autophagy modulation and may point to the potential application of Nano-C60 in adjunct chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Autophagy / physiology*
  • Autophagy / radiation effects
  • Autophagy-Related Protein 5
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / radiation effects
  • Drug Screening Assays, Antitumor
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / radiation effects
  • Fullerenes / chemistry*
  • Fullerenes / pharmacology*
  • Humans
  • Light
  • Mice
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / metabolism
  • Nanoparticles / chemistry*
  • Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism

Substances

  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Fullerenes
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • light chain 3, human
  • Doxorubicin
  • fullerene C60
  • Cisplatin