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

Ghazaryan, N.; Movsisyan, N.; Macedo, J. C.; Vaz, S.; Ayvazyan, N.; Pardo, L.; Logarinho, E.

doi:10.1007/s10637-019-00734-2

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Journal Article

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

MPS-Authors

Ghazaryan, N.
Max Planck Society;

Movsisyan, N.
Max Planck Society;

Macedo, J. C.
Max Planck Society;

Vaz, S.
Max Planck Society;

Ayvazyan, N.
Max Planck Society;

Pardo, L.
Max Planck Society;

Logarinho, E.
Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/30680583
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Citation

Ghazaryan, N., Movsisyan, N., Macedo, J. C., Vaz, S., Ayvazyan, N., Pardo, L., et al. (2019). The antitumor efficacy of monomeric disintegrin obtustatin in S-180 sarcoma mouse model. Invest New Drugs, 37(5), 1044-1051. doi:10.1007/s10637-019-00734-2.

Cite as: https://hdl.handle.net/21.11116/0000-0009-F257-4

Abstract

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 alpha1beta1 integrin to collagen IV. Its oncostatic effect is due to the inhibition of angiogenesis, likely through alpha1beta1 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.