Synergistic anti-tumor effects of arsenic trioxide and blue LED irradiation on human osteosarcoma

Int J Biol Sci. 2019 Jan 1;15(2):386-394. doi: 10.7150/ijbs.28356. eCollection 2019.

Abstract

Arsenic trioxide (ATO) has been well recognized as an anti-tumor agent for various human cancers. Recently, the blue light emitting diodes (LEDs)-based therapy has also been demonstrated to be potential therapeutic strategies for several cancers. However, the combination effects of ATO and blue LED on tumor suppression are still unclear. In this study, we determined whether combination of ATO and blue LED irradiation at 470 nm in wavelength exhibited superior anti-tumor activity in human osteosarcoma (OS). We observed that combination treatments of ATO and blue LED much more significantly decreased the percentages of proliferative cells, and increased apoptotic rate compared with any single treatments in U-2 OS cells. Furthermore, we found suppression of cell migration and invasion were much more pronounced in ATO plus blue LED treated group than single treated groups. Moreover, reactive oxygen species (ROS) assay and immunostaining of γ-H2A.X and p53 indicated that the combined treatments resulted in further markedly increases in ROS accumulation, DNA damage and p53 activity. Taken together, our study demonstrated synergistical anti-tumor effects of combined treatments of ATO and blue LED on human OS cells, which were associated with an increased ROS accumulation, DNA damaged mediated p53 activation.

Keywords: Arsenic trioxide (ATO); Blue LED irradiation; DNA damage; Osteosarcoma (OS); p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Arsenic Trioxide / pharmacology*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • DNA Damage / drug effects*
  • DNA Damage / radiation effects*
  • Humans
  • In Situ Nick-End Labeling
  • Osteosarcoma / metabolism*
  • Reactive Oxygen Species / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Reactive Oxygen Species
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Arsenic Trioxide