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Related Experiment Videos

Proteomic analysis identifies oxidative stress induction by adaphostin.

Luke H Stockwin1, Maja A Bumke, Sherry X Yu

  • 1Developmental Therapeutics Program, Science Applications International Corporation Frederick, Frederick, Maryland 21702, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 19, 2007
PubMed
Summary
This summary is machine-generated.

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Adaphostin induces oxidative stress, leading to apoptosis and Bcr/abl degradation in leukemia cells. Its mechanism involves a redox-active hydroquinone group, not just Bcr/abl inhibition, suggesting it

Area of Science:

  • Proteomics
  • Molecular Biology
  • Cancer Research

Background:

  • Adaphostin (NSC 680410) has known activities beyond Bcr/abl inhibition.
  • Its precise mechanism of action remains incompletely understood.
  • Previous research has described it as 'a drug in search of a mechanism'.

Purpose of the Study:

  • To elucidate the mechanism of action of adaphostin.
  • To investigate adaphostin's effects on myeloid leukemia cell lines using proteomic analysis.
  • To determine if adaphostin's redox-active hydroquinone group contributes to its activity.

Main Methods:

  • Proteomic analysis of HL60 and K562 myeloid leukemia cell lines treated with adaphostin.
  • Two-dimensional PAGE, trypsin digestion, and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Related Experiment Videos

  • Comparative proteomic analysis using hydroquinone (1,4-dihydroxybenzene) and hydrogen peroxide (H2O2) to assess the role of the hydroquinone group and oxidative stress.

    • Main Results:

    • Identified 49 differentially expressed proteins in adaphostin-treated cells, many involved in oxidative stress response and apoptosis.
    • Antioxidant N-acetylcysteine prevented most protein modulations.
    • GSTP1 and Cu/Zn superoxide dismutase (SOD) were identified as adaphostin resistance genes.
    • Hydroquinone and H2O2 treatments mimicked adaphostin's effects, including Bcr/abl degradation, indicating a reactive oxygen species (ROS)-dependent mechanism.

    Conclusions:

    • Adaphostin's mechanism involves inducing oxidative stress via its redox-active hydroquinone group.
    • Kinase inhibition by adaphostin is a reactive oxygen species (ROS)-dependent phenomenon.
    • Adaphostin should be classified as a redox-active-substituted dihydroquinone.