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

Narine Ghazaryan1,2, Naira Movsisyan3,4, Joana Catarina Macedo5

  • 1Laboratory of Toxinology and Molecular Systematics, L.A. Orbeli Institute of Physiology, 0028, Yerevan, Armenia. naringhazaryan@gmail.com.

Investigational New Drugs
|January 26, 2019
PubMed

Insights

Obtustatin, a snake venom peptide, shows promise in treating sarcoma by inhibiting tumor growth and angiogenesis. This disintegrin demonstrated significant anti-cancer effects in mice with low toxicity.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Obtustatin is a short monomeric disintegrin from Levantine Viper snake venom (Macrovipera lebetina obtusa - MLO).
  • It specifically inhibits the α1β1 integrin-collagen IV interaction.
  • Its oncostatic effect is linked to inhibiting angiogenesis via α1β1 integrin in endothelial cells.

Purpose of the Study:

  • To explore the therapeutic potential of obtustatin for sarcoma treatment.
  • To evaluate its anti-angiogenic and anti-tumor effects in vitro and in vivo.

Main Methods:

  • In vivo studies using S-180 sarcoma-bearing mice.
  • In vitro studies on human dermal microvascular endothelial cells (HMVEC-D).
  • Chick embryo chorioallantoic membrane (CAM) assay for anti-angiogenic activity.

Main Results:

  • Obtustatin inhibited tumor growth by 33% in vivo.
  • Vascular endothelial growth factor (VEGF) expression increased post-treatment; caspase 8 levels remained unchanged.
  • Obtustatin inhibited FGF2-induced angiogenesis in the CAM assay and showed no cytotoxicity in HMVEC-D cells.

Conclusions:

  • Obtustatin demonstrates significant anti-tumor and anti-angiogenic activity.
  • It may be a potential therapeutic candidate for sarcoma treatment with low toxicity.
Keywords:
AngiogenesisObtustatinSarcomaVEGF

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