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Related Experiment Videos

DNA damage-mediated apoptosis induced by selenium compounds.

Nai Zhou1, Hai Xiao, Tsai-Kun Li

  • 1Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

The Journal of Biological Chemistry
|May 27, 2003
PubMed
Summary

Selenium compounds like selenite induce tumor cell death through apoptosis. This study reveals selenite-induced apoptosis involves DNA damage, activating ATM/ATR and DNA topoisomerase II (Top II).

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Selenium (Se) compounds are extensively studied for cancer chemoprevention.
  • Apoptosis, or programmed cell death, is a key mechanism in tumor suppression.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying selenite-induced apoptosis.
  • To determine the role of DNA damage and specific regulators in selenite-induced cell death.

Main Methods:

  • Utilized NIH 3T3 and HL-60 cell lines, including Top II-deficient cells.
  • Employed small interfering RNA (siRNA) targeting ATM.
  • Assessed poly(ADP-ribose) polymerase cleavage and H2AX phosphorylation.
  • Investigated DNA topoisomerase II (Top II) activity in vitro and in cells.

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Main Results:

  • Selenite-induced apoptosis was reduced by ATM inhibition, indicating ATM involvement.
  • Selenite treatment stimulated phosphorylation of H2AX, a substrate of ATM/ATR.
  • Selenite-induced apoptosis was diminished in Top II-deficient cells and with a Top II inhibitor.
  • Selenite formed reversible Top II cleavage complexes in vitro.

Conclusions:

  • Selenite-induced apoptosis involves DNA damage.
  • The DNA damage response pathways, including ATM/ATR, are activated by selenite.
  • DNA topoisomerase II (Top II) plays a critical role in selenite-induced apoptosis.