Sulfonyl chromen-4-ones (CHW09) shows an additive effect to inhibit cell growth of X-ray irradiated oral cancer cells, involving apoptosis and ROS generation

Int J Radiat Biol. 2019 Sep;95(9):1226-1235. doi: 10.1080/09553002.2019.1625490. Epub 2019 Jun 17.

Abstract

Purpose: This study evaluates the growth inhibiting potential of our previously described sulfonyl chromen-4-ones (CHW09) compound in X-ray irradiated oral cancer cells. Materials and methods: The growth inhibiting effect and mechanism of combined CHW09/X-ray treatment was examined by analyzing cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), and DNA damage. Results: Individual treatments of CHW09 (10 μg/mL) and X-ray irradiation (12 Gy) slightly decreased cell viability of oral cancer Ca9-22 (87.25% and 86.54%) and CAL 27 (80.00% and 74.01%) cells and normal oral HGF-1 cells (92.76% and 87.56%) at 24 h-MTS assay, respectively. In a combined treatment (CHW09/X-ray), the cell viability in Ca9-22 and CAL 27 cells was significantly decreased to 73.48% and 59.07%, whereas HGF-1 cells maintained 84.97% viability in 24 h-MTS assay. For CAL 27 cells, both 72 h-MTS assay and clonogenic assay showed that CHW09/X-ray resulted in more growth inhibition than other treatments. Intracellular ROS levels of CHW09/X-ray were higher than for CHW09, X-ray and control. CHW09/X-ray and X-ray alone had higher G2/M arrest than the control and CHW09 alone. Moreover, flow cytometry and western blotting showed that CHW09/X-ray treatment caused higher apoptosis levels. Levels of H2A histone family member X (γH2AX)-based DNA damage and 8-oxo-2'-deoxyguanosine (8-oxodG)-oxidative DNA damage of CHW09/X-ray were higher than for CHW09, X-ray and control. Conclusion: CHW09/X-ray treatment had additive growth inhibiting effects against X-ray irradiated oral cancer cells, partly attributing to apoptosis and ROS generation.

Keywords: X-ray; chromones; oral cancer; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Humans
  • Mouth Neoplasms / pathology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Reactive Oxygen Species / metabolism*
  • X-Rays

Substances

  • Benzopyrans
  • Reactive Oxygen Species
  • Caspases