EcTI impairs survival and proliferation pathways in triple-negative breast cancer by modulating cell-glycosaminoglycans and inflammatory cytokines

Cancer Lett. 2020 Oct 28:491:108-120. doi: 10.1016/j.canlet.2020.08.017. Epub 2020 Aug 22.

Abstract

Breast cancer is the most common malignant tumor among women worldwide, and triple-negative breast cancer is the most aggressive type of breast cancer, which does not respond to hormonal therapies. The protease inhibitor, EcTI, extracted from seeds of Enterolobium contortisiliquum, acts on the main signaling pathways of the MDA-MB-231 triple-negative breast cancer cells. This inhibitor, when bound to collagen I of the extracellular matrix, triggers a series of pathways capable of decreasing the viability, adhesion, migration, and invasion of these cells. This inhibitor can interfere in the cell cycle process through the main signaling pathways such as the adhesion, Integrin/FAK/SRC, Akt, ERK, and the cell death pathway BAX and BCL-2. It also acts by reducing the main inflammatory cytokines such as TGF-α, IL-6, IL-8, and MCP-1, besides NFκB, a transcription factor, responsible for the aggressive and metastatic characteristics of this type of tumor. Thus, the inhibitor was able to reduce the main processes of carcinogenesis of this type of cancer.

Keywords: Collagen; Inflammation; Metalloprotease; Metastasis; Protease inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Collagen Type I / metabolism
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Fabaceae / chemistry*
  • Female
  • Glycosaminoglycans / metabolism*
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Trypsin Inhibitors / pharmacology*
  • Trypsin Inhibitors / therapeutic use

Substances

  • Collagen Type I
  • Cytokines
  • Glycosaminoglycans
  • Trypsin Inhibitors
  • Matrix Metalloproteinases