Cobalt oxide nanoparticles induced oxidative stress linked to activation of TNF-α/caspase-8/p38-MAPK signaling in human leukemia cells

J Appl Toxicol. 2015 Jun;35(6):603-13. doi: 10.1002/jat.3080. Epub 2015 Jan 11.

Abstract

The purpose of this study was to determine the intracellular signaling transduction pathways involved in oxidative stress induced by nanoparticles in cancer cells. Activation of reactive oxygen species (ROS) has some therapeutic benefits in arresting the growth of cancer cells. Cobalt oxide nanoparticles (CoO NPs) are an interesting compound for oxidative cancer therapy. Our results showed that CoO NPs elicited a significant (P <0.05) amount of ROS in cancer cells. Co-treatment with N-aceyltine cystine (an inhibitor of ROS) had a protective role in cancer cell death induced by CoO NPs. In cultured cells, the elevated level of tumor necrosis factor-alpha (TNF-α) was noted after CoO NPs treatment. This TNF-α persuaded activation of caspase-8 followed by phosphorylation of p38 mitogen-activated protein kinase and induced cell death. This study showed that CoO NPs induced oxidative stress and activated the signaling pathway of TNF-α-Caspase-8-p38-Caspase-3 to cancer cells.

Keywords: ROS; TNF-α; cancer; cobalt oxide nanoparticles; p38-MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Caspase 8 / physiology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cobalt / adverse effects*
  • Humans
  • Leukemia, Experimental / drug therapy*
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Metal Nanoparticles / adverse effects*
  • Mice
  • Microscopy, Electron, Transmission
  • Neoplasm Transplantation
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Oxides / adverse effects*
  • Reactive Oxygen Species / metabolism
  • Spectroscopy, Fourier Transform Infrared
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Oxides
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Cobalt
  • Caspase 8
  • cobalt oxide
  • Acetylcysteine