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Onconase, an anti-tumor ribonuclease suppresses intracellular oxidative stress

B Ardelt1, G Juan, P Burfeind

  • 1Alfacell Corporation, Bloomfield, NJ 07003, USA. bardelt@alfacell.com

International Journal of Oncology
|August 3, 2007
PubMed

Insights

Onconase (ONC), a frog-derived antitumor enzyme, reduces intracellular oxidants in cancer cells by decreasing their generation and increasing degradation. This antioxidant activity contributes to ONC

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Onconase (ONC) is an antitumor ribonuclease with apoptosis-inducing properties.
  • Reactive oxygen intermediates (ROI) modulate drug cytotoxicity.
  • ONC exhibits synergistic effects with other anticancer agents.

Purpose of the Study:

  • To investigate the effects of Onconase on intracellular ROI levels in normal and tumor cell lines.
  • To elucidate the mechanism underlying ONC's influence on cellular redox balance.
  • To correlate ONC's antioxidant activity with its cytotoxic and apoptotic effects.

Main Methods:

  • Cell culture of normal and tumor cell lines.
  • Measurement of intracellular ROI levels.
  • Assessment of mitochondrial transmembrane potential and ATP generation.
  • Analysis of Bcl-2 and Bax protein expression.

Main Results:

  • ONC significantly decreased intracellular ROI levels in all studied cell lines.
  • This reduction in ROI was dependent on ONC's ribonucleolytic activity.
  • ONC decreased mitochondrial potential, ATP generation, and modulated Bcl-2/Bax expression, promoting apoptosis.
  • ONC's effects were linked to interference with cellular redox regulation.

Conclusions:

  • Onconase possesses significant antioxidant activity, reducing ROI generation and accelerating degradation.
  • The observed antioxidant properties of ONC are integral to its cytotoxic mechanism against cancer cells.
  • ONC exerts its biological effects by modulating the cellular redox system, impacting apoptosis pathways.

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