A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders
2011

A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

publication Evidence: moderate

Author Information

Author(s): Huwiler Andrea, Bourquin Florence, Kotelevets Nataliya, Pastukhov Oleksandr, Capitani Guido, Grütter Markus G., Zangemeister-Wittke Uwe

Primary Institution: Institute of Pharmacology, University of Bern, Bern, Switzerland

Hypothesis

Can the prokaryotic S1P lyase from Symbiobacterium thermophilum effectively degrade extracellular S1P and mitigate pathophysiological processes associated with increased levels of S1P?

Conclusion

Recombinant StSPL effectively degrades extracellular S1P in vitro and in vivo, showing potential as a therapeutic enzyme for diseases associated with elevated S1P levels.

Supporting Evidence

  • StSPL was shown to effectively degrade S1P in cell culture medium and in blood.
  • Intravenous injection of StSPL in mice resulted in a 70% decline in plasma S1P levels within 1 hour.
  • StSPL disrupted S1P receptor signaling in various cell types, inhibiting proliferation and migration.
  • StSPL treatment reduced tumor cell-induced angiogenesis in the chicken chorioallantoic membrane model.

Takeaway

Scientists found a way to use a special enzyme from bacteria to break down a substance in the body that can cause diseases like cancer and inflammation.

Methodology

The study involved biochemical characterization of StSPL, in vitro assays on various cell types, and in vivo experiments in mice and chicken chorioallantoic membranes.

Limitations

The transient nature of S1P degradation in vivo suggests that continuous production of S1P may limit the effectiveness of StSPL.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0022436

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