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Interferon enhances the activity of the anticancer ribonuclease, onconase
V M Vasandani1, J C Castelli, J S Hott
1Biochemistry Section, Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892-1414, USA.
Abstract:
Interferons (IFN) are biologic agents involved in the antiviral response and the inhibition of tumor growth. Biochemical pathways of IFN action include the double-stranded RNA-activated oligoadenylate synthetase, RNase L, and double-stranded RNA-dependent protein kinase (PKR). Extracellular ribonucleases, especially onconase, also display antiviral and antitumor properties and involve degradation of RNA. We find that IFN increases the anticancer activity of onconase. These two agents work synergistically, and the effect is seen at the level of translation probably because of the degradation of tRNA.
Insights
Interferons (IFN) enhance the anticancer effects of onconase, a biologic agent. This synergy, observed at the translational level, likely involves tRNA degradation, boosting antiviral and antitumor responses.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Interferons (IFN) are crucial biologic agents mediating antiviral responses and tumor growth inhibition.
- Key IFN pathways involve RNase L and protein kinase R (PKR).
- Extracellular ribonucleases like onconase exhibit antiviral and antitumor properties via RNA degradation.
Purpose of the Study:
- To investigate the combined effect of interferons (IFN) and onconase on anticancer activity.
- To elucidate the synergistic mechanisms underlying the enhanced efficacy of these agents.
Main Methods:
- Assessed the impact of IFN on the anticancer activity of onconase.
- Investigated the cellular mechanisms, focusing on translational processes and RNA degradation.
Main Results:
- Interferons significantly increase the anticancer efficacy of onconase.
- The combination of IFN and onconase demonstrates synergistic activity.
- This synergy appears to operate at the translational level, potentially through tRNA degradation.
Conclusions:
- IFN and onconase act synergistically to enhance anticancer effects.
- The observed synergy is likely mediated by the degradation of transfer RNA (tRNA), impacting translation.
- This finding suggests a novel therapeutic strategy combining IFNs with onconase for cancer treatment.