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Int. J. Mol. Sci. 2015, 16(4), 7027-7044; doi:10.3390/ijms16047027

Antiangiogenesis, Loss of Cell Adhesion and Apoptosis Are Involved in the Antitumoral Activity of Proteases from V. cundinamarcensis (C. candamarcensis) in Murine Melanoma B16F1

1
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil
2
Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil
3
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil
4
Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 10 January 2015 / Revised: 6 March 2015 / Accepted: 11 March 2015 / Published: 27 March 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

The proteolytic enzymes from V. cundinamarcensis latex, (P1G10), display healing activity in animal models following various types of lesions. P1G10 or the purified isoforms act as mitogens on fibroblast and epithelial cells by stimulating angiogenesis and wound healing in gastric and cutaneous ulcers models. Based on evidence that plant proteinases act as antitumorals, we verified this effect on a murine melanoma model. The antitumoral effect analyzed mice survival and tumor development after subcutaneous administration of P1G10 into C57BL/6J mice bearing B16F1 low metastatic melanoma. Possible factors involved in the antitumoral action were assessed, i.e., cytotoxicity, cell adhesion and apoptosis in vitro, haemoglobin (Hb), vascular endothelial growth factor (VEGF), tumor growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) content and N-acetyl-glucosaminidase (NAG) activity. We observed that P1G10 inhibited angiogenesis measured by the decline of Hb and VEGF within the tumor, and TGF-β displayed a non-significant increase and TNF-α showed a minor non-significant reduction. On the other hand, there was an increase in NAG activity. In treated B16F1 cells, apoptosis was induced along with decreased cell binding to extracellular matrix components (ECM) and anchorage, without impairing viability. View Full-Text
Keywords: proteases; V. cundinamarcensis; antitumoral; melanoma B16F1; apoptosis; anchorage loss proteases; V. cundinamarcensis; antitumoral; melanoma B16F1; apoptosis; anchorage loss
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dittz, D.; Figueiredo, C.; Lemos, F.O.; Viana, C.T.R.; Andrade, S.P.; Souza-Fagundes, E.M.; Fujiwara, R.T.; Salas, C.E.; Lopes, M.T.P. Antiangiogenesis, Loss of Cell Adhesion and Apoptosis Are Involved in the Antitumoral Activity of Proteases from V. cundinamarcensis (C. candamarcensis) in Murine Melanoma B16F1. Int. J. Mol. Sci. 2015, 16, 7027-7044.

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