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

International Journal of Molecular Sciences

Dalton Dittz³  Cinthia Figueiredo³  Fernanda O. Lemos³  Celso T. R. Viana¹  Silvia P. Andrade¹  Elaine M. Souza-Fagundes¹  Ricardo T. Fujiwara²  Carlos E. Salas⁴  Miriam T. P. Lopes³ 

[1] Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil; E-Mails:;Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil; E-Mail:;Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil; E-Mails:;Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil

关键词: proteases;    V. cundinamarcensis;    antitumoral;    melanoma B16F1;    apoptosis;    anchorage loss;   

DOI  :  10.3390/ijms16047027

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.