Pro-apoptotic effect of new quinolone 7- ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate on cervical cancer cell line HeLa alone/with UVA irradiation

Toxicol In Vitro. 2016 Jun:33:35-44. doi: 10.1016/j.tiv.2016.02.012. Epub 2016 Feb 23.

Abstract

7- ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo [3,4-h]quinoline-7-carboxylate (E2h) is a new synthetically prepared quinolone derivative, which in our primary study showed cytotoxic effects towards tumor cells. The aim of the present study was to examine the antiproliferative and apoptosis inducing activities of E2h towards human cervical cancer cell line HeLa with/without the presence of UVA irradiation. Further, the molecular mechanism involved in E2h-induced apoptosis in HeLa cells was investigated. Our results showed that both non-photoactivated and photoactivated E2h caused morphological changes and inhibited the cell growth of HeLa cells in a time- and dose-dependent manner. Irradiation increased the sensitivity of HeLa cells to E2h. Quinolone induced S and G2/M arrest and apoptosis in HeLa cells, as characterized by DNA fragmentation and flow cytometry. In addition, E2h elevated the level of reactive oxygen species and activated caspases 3. In conclusions, E2h alone/in combination with UVA irradiation induced apoptosis in HeLa cells through the ROS-mitochondrial/caspase 3-dependent pathway.

Keywords: Apoptosis; Cell cycle arrest; HeLa cells; Quinolone derivative; UVA irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Female
  • HeLa Cells
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potential, Mitochondrial / radiation effects
  • Organoselenium Compounds / pharmacology*
  • Quinolones / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Ultraviolet Rays*
  • Uterine Cervical Neoplasms

Substances

  • 7-ethyl 9-ethyl-6-oxo-6,9-dihydro(1,2,5)selenadiazolo(3,4-h)quinoline-7-carboxylate
  • Antineoplastic Agents
  • Organoselenium Compounds
  • Quinolones
  • Reactive Oxygen Species