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Pasteurella multocida toxin is a potent activator of anti-apoptotic signalling pathways

Inga Preuss1, Dagmar Hildebrand, Joachim H C Orth

  • 1Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.

Cellular Microbiology
|March 25, 2010
PubMed

Insights

Toxigenic Pasteurella multocida toxin (PMT) prevents cancer cell death by activating survival pathways like PI3K/Akt and Pim-1. This anti-apoptotic effect supports PMT's potential role in cancer development.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Toxigenic Pasteurella multocida produces a 146 kDa protein toxin (PMT) with high mitogenic activity, suggesting carcinogenic potential.
  • PMT disrupts host cell signaling by constitutively activating heterotrimeric G proteins, impacting pathways crucial for cell growth and death.

Purpose of the Study:

  • To investigate the anti-apoptotic mechanisms of PMT in human cells.
  • To determine if PMT's anti-apoptotic activity contributes to its proposed carcinogenic properties.

Main Methods:

  • HEK293 cells and human cancer cell lines were treated with PMT.
  • Apoptosis was induced using staurosporine and chemotherapeutic agents.
  • Western blotting and kinase assays were used to assess signaling pathway activation (e.g., Akt, Pim-1, RhoA, STATs).

Main Results:

  • PMT treatment inhibited staurosporine-induced apoptosis in HEK293 cells via PI3K-dependent Akt phosphorylation and constitutive Pim-1 kinase expression.
  • PMT activated pro-survival pathways (GSK3beta, Mcl-1, Bcl-xL, Bcl-2) and downregulated pro-apoptotic signals (Bax, Puma).
  • PMT blocked apoptosis induced by chemotherapeutic agents in human cancer cell lines.

Conclusions:

  • PMT acts as a potent anti-apoptotic agent by promoting pro-survival kinase signaling.
  • The anti-apoptotic effects of PMT provide evidence for its potential carcinogenic role.

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