Regulation of cellular and molecular markers of epithelial-mesenchymal transition by Brazilin in breast cancer cells

PeerJ. 2024 May 9:12:e17360. doi: 10.7717/peerj.17360. eCollection 2024.

Abstract

Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future.

Keywords: Brazilin; Breast cancer; Cell invasion; E-cadherin; MMP-2; MMP-9; Vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzopyrans* / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cadherins* / metabolism
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition* / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness / genetics
  • Nuclear Proteins
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Twist-Related Protein 1* / genetics
  • Twist-Related Protein 1* / metabolism
  • Vimentin* / genetics
  • Vimentin* / metabolism

Substances

  • brazilin
  • Cadherins
  • Vimentin
  • Twist-Related Protein 1
  • Benzopyrans
  • TWIST1 protein, human
  • Biomarkers, Tumor
  • Matrix Metalloproteinases
  • Nuclear Proteins

Grants and funding

This work was supported by grants from COCYTIEG awarded to Jorge Bello-Martinez and SEP-PROMEP/103.5/14/11118 (UAGro- PTC 053) and SEP-CONACYT CB-2014-01-239870 awarded to Napoleon Navarro-Tito. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.