title: Antiangiogenesis, loss of cell adhesion and apoptosis are involved in the antitumoral activity of Proteases from V. cundinamarcensis (C. candamarcensis) in murine melanoma B16F1.
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.
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. daltondittz@gmail.com.
authors.forename: Dalton
authors.initials: D
authors.lastname: Dittz
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. cinthiafigueiredo@yahoo.com.br.
authors.forename: Cinthia
authors.initials: C
authors.lastname: Figueiredo
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. folemos@hotmail.com.
authors.forename: Fernanda O
authors.initials: FO
authors.lastname: Lemos
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. celsotarso@gmail.com.
authors.forename: Celso T R
authors.initials: CT
authors.lastname: Viana
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. andrades@icb.ufmg.br.
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Andrade
authors.affiliation: Departamento de Fisiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. fujiwara@icb.ufmg.br.
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Fujiwara
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. cesbufmg@icb.ufmg.br.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Salas
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. mtpl@icb.ufmg.br.
authors.forename: Miriam T P
authors.initials: MT
authors.lastname: Lopes
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D029441:Carica / Q000201:enzymology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010447:Peptide Hydrolases / Q000008:administration & dosage* / Q000494:pharmacology; D010940:Plant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D010940:Plant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010447:Peptide Hydrolases
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