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Updated: May 30, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Stabilisation of p53 enhances reovirus-induced apoptosis and virus spread through p53-dependent NF-κB activation

D Pan1, L-Z Pan, R Hill

  • 1Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.

British Journal of Cancer
|August 25, 2011
PubMed
Abstract

Insights

Nutlin-3a enhances reovirus cancer therapy by boosting p53-dependent apoptosis and virus spread. This combination shows promise for treating cancers with wild-type p53.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Naturally oncolytic reovirus shows promise as a cancer therapeutic due to its selective killing of cancer cells.
  • Tumour suppressor p53 mutations are common in cancers, but its role in reovirus oncolysis is not well understood.

Purpose of the Study:

  • To investigate the role of p53 in reovirus-mediated cancer cell killing.
  • To explore the potential of combining reovirus with Nutlin-3a, a p53 stabilizer, for enhanced cancer therapy.

Main Methods:

  • Human cancer cell lines were treated with Nutlin-3a, reovirus, or both.
  • Assays included reovirus titration, western blot, real-time PCR, apoptosis assays (Annexin V/7-AAD), and confocal microscopy for NF-κB p65 translocation.

Main Results:

  • Nutlin-3a stabilized p53, significantly enhancing reovirus-induced apoptosis and virus release, without affecting reovirus replication.
  • Enhanced apoptosis was p53-dependent, requiring increased Bax and p21 expression.
  • Elevated NF-κB activation was crucial for the enhanced apoptosis, as NF-κB inhibitors abolished the synergistic effect.

Conclusions:

  • Nutlin-3a treatment boosts reovirus-induced apoptosis and spread via p53-dependent NF-κB activation.
  • Combining reovirus and Nutlin-3a may offer an improved therapeutic strategy for cancers with wild-type p53.

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