The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in

Magdalena Cal1, Irwin Matyjaszczyk1, Ireneusz Litwin2

  • 1Department of Mycology and Genetics, Institute of Genetics and Microbiology, University of Wroclaw, 51-148 Wroclaw, Poland.

Cells
|May 14, 2020
PubMed

Insights

Low concentrations of 3-bromopyruvate (3-BP) induce DNA damage in cancer cells and yeast, likely through reactive oxygen species (ROS) generation. This DNA damage triggers cell cycle arrest, offering potential for novel anticancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • 3-bromopyruvate (3-BP) is a small molecule with known anticancer properties.
  • Cancer cells overexpress monocarboxylate transporters (MCTs) for selective 3-BP uptake.
  • 3-BP affects cancer cell metabolism by inhibiting key enzymes, depleting ATP, and generating reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the impact of 3-BP on DNA integrity at specific concentrations.
  • To explore the mechanisms underlying 3-BP-induced DNA damage.
  • To assess the potential of 3-BP as a DNA-damaging agent in cancer therapy.

Main Methods:

  • Treatment of yeast and human cancer cells with 3-BP.
  • Analysis of DNA damage markers, including double-strand breaks and H2A.X phosphorylation.
  • Cell cycle analysis to determine the phase-specific effects of 3-BP.

Main Results:

  • 3-BP induces DNA damage in both yeast and human cancer cells at low concentrations.
  • DNA double-strand breaks are generated in yeast during the S-phase of the cell cycle.
  • 3-BP treatment leads to DNA damage, checkpoint activation, and H2A.X phosphorylation in human cancer cells.

Conclusions:

  • 3-BP at low concentrations can induce significant DNA damage, likely via ROS generation.
  • This DNA damage response is cell cycle-dependent in yeast and involves key signaling pathways in human cancer cells.
  • Understanding 3-BP's DNA-damaging effects provides insights for developing targeted anticancer therapies.

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