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Novel Fusion Protein Derived from Vasostatin 30 and Vasoinhibin II-14.1 Potently Inhibits Coronary Endothelial Cell Proliferation

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Abstract

Angiogenesis has been considered an important target for cancer therapy. The inhibition of angiogenesis represents a promising strategy for anti-cancer treatment, tumor growth inhibition, and metastasis. Vasostatin 30 (Vs30), and the 14.1 kDa vasoinhibin (Vi-II-14.1) are two peptides with remarkable anti-tumor and anti-angiogenic effect. The aim of this study was to produce a novel fusion protein between Vs30 and Vi-II-14.1, denominated VS_VI, to obtain a new protein with higher biological activity. The protein fusion genes were cloned into a T7 promoter-based vector, expressed in Escherichia coli BL21-SI and purified by affinity column chromatography. In vitro assays showed that the recombinant fusion protein inhibited rat coronary endothelial cell proliferation at 65.5 % at 10 nM, whereas recombinant Vs30 and Vi-II-14.1 inhibited at 33 and 50.5 % respectively, at the same concentration. The results showed that VS_VI is significantly more active than the Vs30 and Vi-II-14.1 separately. In addition, a practical classification of the vasoinhibins based on the peptide origin and theoretical molecular weight is proposed. This is the first study to produce a new fusion protein derived from Vs30 and Vi-II-14.1, both of them proposed as promising therapeutic agents.

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Acknowledgments

We thank Dr. Carmen Clapp and Dr. Gabriel Nava from the Instituto de Neurobiología, UNAM for the pSG-hPRL plasmid, and Héctor Rosas Hernández (UASLP) and Leandro G. Ordóñez Acevedo (IPICyT) for technical assistance. G. Vazquez thanks CONACyT for her scholarship No. 211450. We thank Jennifer Eckerly Goss for the English revision. The sponsors had no role in study design, in the collection, analysis, and interpretation of data, in writing the report or in the decision to submit the paper for publication.

Disclosure

This work was supported partially by CONACyT-BASICAS 82010 and PROMEP/103.5/072574.

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Authors and Affiliations

  1. División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica, Camino a la Presa San José Nº 2055 Lomas 4a sección, CP 78216, San Luis Potosí, SLP, Mexico

    Gabriela Vazquez Rodriguez & Antonio De Leon Rodriguez

  2. Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava Nº 6, CP 78210, San Luis Potosí, SLP, Mexico

    Carmen Gonzalez

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  1. Gabriela Vazquez Rodriguez
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  2. Carmen Gonzalez
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Correspondence to Antonio De Leon Rodriguez.

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Vazquez Rodriguez, G., Gonzalez, C. & De Leon Rodriguez, A. Novel Fusion Protein Derived from Vasostatin 30 and Vasoinhibin II-14.1 Potently Inhibits Coronary Endothelial Cell Proliferation. Mol Biotechnol 54, 920–929 (2013). https://doi.org/10.1007/s12033-012-9642-4

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