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The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model

  • Narine GhazaryanEmail author
  • Naira Movsisyan
  • Joana Catarina Macedo
  • Sara Vaz
  • Naira Ayvazyan
  • Luis Pardo
  • Elsa Logarinho
PHASE I STUDIES
  • 49 Downloads

Summary

Obtustatin, isolated from the Levantine Viper snake venom (Macrovipera lebetina obtusa -MLO), is the shortest known monomeric disintegrin shown to specifically inhibit the binding of the α1β1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through α1β1 integrin inhibition in endothelial cells. To explore the therapeutic potential of obtustatin, we studied its effect in S-180 sarcoma-bearing mice model in vivo as well as in human dermal microvascular endothelial cells (HMVEC-D) in vitro, and tested anti-angiogenic activity in vivo using the chick embryo chorioallantoic membrane assay (CAM assay). Our in vivo results show that obtustatin inhibits tumour growth by 33%. The expression of vascular endothelial growth factor (VEGF) increased after treatment with obtustatin, but the level of expression of caspase 8 did not change. In addition, our results demonstrate that obtustatin inhibits FGF2-induced angiogenesis in the CAM assay. Our in vitro results show that obtustatin does not exhibit cytotoxic activity in HMVEC-D cells in comparison to in vivo results. Thus, our findings disclose that obtustatin might be a potential candidate for the treatment of sarcoma in vivo with low toxicity.

Keywords

Obtustatin Sarcoma Angiogenesis VEGF 

Notes

Funding

This work was made possible by the research grant # molbio 3440 from the Armenian National Science and Education Fund (ANSEF) based in New York.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Narine Ghazaryan
    • 1
    • 2
    Email author
  • Naira Movsisyan
    • 2
    • 3
  • Joana Catarina Macedo
    • 4
  • Sara Vaz
    • 4
  • Naira Ayvazyan
    • 1
  • Luis Pardo
    • 2
  • Elsa Logarinho
    • 4
  1. 1.Laboratory of Toxinology and Molecular SystematicsL.A. Orbeli Institute of PhysiologyYerevanArmenia
  2. 2.Oncophysiology GroupMax Planck Institute for Experimental MedicineGöttingenGermany
  3. 3.Göttingen Graduate School for Neurosciences, Biophysics, and Molecular BiosciencesGöttingenGermany
  4. 4.Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular, Instituto de Investigação e Inovação em Saúde – i3SUniversidade do PortoPortoPortugal

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