Zn-doped CuO nanocomposites inhibit tumor growth by NF-κB pathway cross-linked autophagy and apoptosis

Nanomedicine (Lond). 2019 Jan;14(2):131-149. doi: 10.2217/nnm-2018-0366. Epub 2018 Nov 5.

Abstract

Aim: To investigate the antitumor effects and action mechanism of Zn-doped CuO nanocomposites (Zn-CuONPs).

Materials & methods: Therapeutic effects and mechanisms of Zn-CuONPs were investigated both in vitro and in vivo.

Results: Zn-CuONPs could inhibit tumor growth both in vitro and in vivo significantly. Zn-CuONPs treatment resulted in cytotoxicity, reactive oxygen species (ROS) production, DNA damage, apoptosis and autophagy. ROS scavenger N-acetylcysteine attenuated all of the above effects induced by Zn-CuONPs. N-acetylcysteine also restored the effects of Zn-CuONPs on protein expressions related to apoptosis, autophagy and NF-κB pathways. NF-κB pathway inhibitor pyrrolidine dithiocarbamate significantly attenuated Zn-CuONPs induced apoptosis and autophagy.

Conclusion: Our data demonstrated that Zn-CuONPs could inhibit tumor growth both in vitro and in vivo by ROS-dependent apoptosis and autophagy cross-linked by NF-κB pathways.

Keywords: -acetylcysteine; NF-κB pathways; Zn-doped CuO nanocomposites; apoptosis; autophagy; cancer therapy; cytotoxicity; nanoparticles; reactive oxygen species; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / chemistry
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Copper / chemistry*
  • Humans
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism*
  • Nanocomposites / chemistry*
  • Pyrrolidines / chemistry
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Thiocarbamates / chemistry
  • Zinc / chemistry*

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Pyrrolidines
  • Reactive Oxygen Species
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid
  • Copper
  • Zinc
  • cupric oxide
  • Acetylcysteine