Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma
Abstract Based on available evidence showing the antitumoral/antimetastatic activity of the proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, we analyze possible mechanisms involved in the antimetastasic effect of this fraction and subfractions (CMS1, CMS2) after incubation with B16F1...
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Nature Portfolio
2025-07-01
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| author | Dalton Dittz Isabela Paula Nunes Hortência Maciel de Castro Oliveira Gustavo Batista de Menezes Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes |
| author_facet | Dalton Dittz Isabela Paula Nunes Hortência Maciel de Castro Oliveira Gustavo Batista de Menezes Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes |
| author_sort | Dalton Dittz |
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| description | Abstract Based on available evidence showing the antitumoral/antimetastatic activity of the proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, we analyze possible mechanisms involved in the antimetastasic effect of this fraction and subfractions (CMS1, CMS2) after incubation with B16F10 melanoma cells in vitro and in vivo under sub-apoptotic conditions. The goal was to investigate potential mediators of the antitumoral/antimetastatic effect of P1G10 triggered before the onset of apoptosis. In B16F10 preincubated viable cells, it was observed changes in adhesion to ECM (extracellular matrix), reduced activity of metalloproteases and invasivity, reduction of pAkt and pErk mostly affecting the rate of lung metastasis in mice injected with B16F10 treated cells. In most of these assays the effects depend of the proteolytic activity of the fractions. Unexpectedly, the CMS2-IAA (CMS2 with proteolytically activity inhibited by iodoacetamide), enhanced pErk phosphorylation and increased procaspase-3 levels. The invasivity of B16F10 was impaired following incubation with the proteolytic fraction without affecting cell viability under the conditions analyzed. In conclusion, CMS2 reduces in vitro cell invasion and metastasis in murine melanoma B16F10. |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-7599e18a1988491fbc164c607cbb048b2025-08-20T03:45:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-024-73489-3Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanomaDalton Dittz0Isabela Paula Nunes1Hortência Maciel de Castro Oliveira2Gustavo Batista de Menezes3Carlos Edmundo Salas Bravo4Miriam Teresa Paz Lopes5Department of Biochemistry and Pharmacology, Federal University of PiauíDepartment of Pharmacology, Federal University of Minas GeraisDepartment of Morphology, Federal University of Minas GeraisDepartment of Morphology, Federal University of Minas GeraisDepartmente of Biochemistry and Immunology, Federal University of Minas GeraisDepartment of Pharmacology, Federal University of Minas GeraisAbstract Based on available evidence showing the antitumoral/antimetastatic activity of the proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, we analyze possible mechanisms involved in the antimetastasic effect of this fraction and subfractions (CMS1, CMS2) after incubation with B16F10 melanoma cells in vitro and in vivo under sub-apoptotic conditions. The goal was to investigate potential mediators of the antitumoral/antimetastatic effect of P1G10 triggered before the onset of apoptosis. In B16F10 preincubated viable cells, it was observed changes in adhesion to ECM (extracellular matrix), reduced activity of metalloproteases and invasivity, reduction of pAkt and pErk mostly affecting the rate of lung metastasis in mice injected with B16F10 treated cells. In most of these assays the effects depend of the proteolytic activity of the fractions. Unexpectedly, the CMS2-IAA (CMS2 with proteolytically activity inhibited by iodoacetamide), enhanced pErk phosphorylation and increased procaspase-3 levels. The invasivity of B16F10 was impaired following incubation with the proteolytic fraction without affecting cell viability under the conditions analyzed. In conclusion, CMS2 reduces in vitro cell invasion and metastasis in murine melanoma B16F10.https://doi.org/10.1038/s41598-024-73489-3MetastasisMelanomaCell adhesionCell invasionCysteine proteases |
| spellingShingle | Dalton Dittz Isabela Paula Nunes Hortência Maciel de Castro Oliveira Gustavo Batista de Menezes Carlos Edmundo Salas Bravo Miriam Teresa Paz Lopes Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma Scientific Reports Metastasis Melanoma Cell adhesion Cell invasion Cysteine proteases |
| title | Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma |
| title_full | Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma |
| title_fullStr | Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma |
| title_full_unstemmed | Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma |
| title_short | Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma |
| title_sort | loss of adhesion impairs invasiveness and cell survival contributing to the antimetastatic effect of cysteine proteases from vasconcella cundinamarcensis in melanoma |
| topic | Metastasis Melanoma Cell adhesion Cell invasion Cysteine proteases |
| url | https://doi.org/10.1038/s41598-024-73489-3 |
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