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Loss of adhesion impairs invasiveness and cell survival, contributing to the antimetastatic effect of cysteine proteases from Vasconcella cundinamarcensis in melanoma

  • 0Department of Biochemistry and Pharmacology, Federal University of Piauí, Teresina, Piauí, Brazil.
Scientific Reports +

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July 1, 2025

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July 1, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Vasconcellea cundinamarcensis fractions reduce melanoma cell invasion and metastasis. Proteolytic activity of CMS2 impairs B16F10 melanoma cell invasivity and lung metastasis in mice without affecting cell viability.

Area Of Science

  • Biochemistry
  • Oncology
  • Pharmacology

Background

  • Vasconcellea cundinamarcensis harbors proteolytic compounds with demonstrated antitumoral and antimetastatic properties.
  • Understanding the precise mechanisms underlying these effects, particularly before apoptosis induction, is crucial for therapeutic development.

Purpose Of The Study

  • To elucidate the antimetastatic mechanisms of a proteolytic fraction (P1G10) and its subfractions (CMS1, CMS2) from Vasconcellea cundinamarcensis against B16F10 melanoma cells.
  • To investigate mediators of antitumoral/antimetastatic effects triggered prior to apoptosis.

Main Methods

  • In vitro and in vivo studies using B16F10 melanoma cells and murine models.
  • Analysis of cell adhesion to extracellular matrix (ECM), metalloprotease activity, invasivity, and levels of phosphorylated Akt (pAkt) and extracellular signal-regulated kinase (pErk).
  • Assessment of cell viability and procaspase-3 levels following treatment with fractions, including a proteolytically inhibited subfraction (CMS2-IAA).

Main Results

  • P1G10 and CMS2 fractions reduced B16F10 cell adhesion to ECM, metalloprotease activity, and invasivity.
  • Treatment led to reduced pAkt and pErk levels, significantly decreasing lung metastasis in mice.
  • Proteolytic activity was essential for these observed antimetastatic effects; CMS2-IAA unexpectedly increased pErk and procaspase-3.
  • CMS2 effectively impaired B16F10 invasivity without compromising cell viability.

Conclusions

  • The proteolytic fraction CMS2 from Vasconcellea cundinamarcensis demonstrates significant potential in reducing in vitro cell invasion and in vivo metastasis of murine melanoma B16F10.
  • These effects are mediated by mechanisms involving altered cell adhesion, reduced protease activity, and modulation of signaling pathways (pAkt, pErk) prior to apoptosis induction.
  • The findings highlight CMS2 as a promising candidate for further investigation in melanoma treatment strategies.

Keywords:

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