1. Antiangiogenesis, loss of cell adhesion and apoptosis are involved in the antitumoral activity of Proteases from V. cundinamarcensis (C. candamarcensis) in murine melanoma B16F1.
- Author
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Dittz D, Figueiredo C, Lemos FO, Viana CT, Andrade SP, Souza-Fagundes EM, Fujiwara RT, Salas CE, and Lopes MT
- Subjects
- Angiogenesis Inhibitors pharmacology, Animals, Antineoplastic Agents, Phytogenic pharmacology, Apoptosis, Cell Adhesion drug effects, Cell Line, Tumor, Male, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, Peptide Hydrolases pharmacology, Plant Proteins administration & dosage, Plant Proteins pharmacology, Skin Neoplasms metabolism, Skin Neoplasms pathology, Transforming Growth Factor beta metabolism, Treatment Outcome, Tumor Necrosis Factor-alpha metabolism, Angiogenesis Inhibitors administration & dosage, Antineoplastic Agents, Phytogenic administration & dosage, Carica enzymology, Melanoma, Experimental drug therapy, Peptide Hydrolases administration & dosage, Skin Neoplasms drug therapy
- 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.
- Published
- 2015
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