The analysis of boric acid effect on epithelial-mesenchymal transition of CD133 + CD117 + lung cancer stem cells

Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6791-6802. doi: 10.1007/s00210-024-03062-2. Epub 2024 Mar 27.

Abstract

Targeting lung cancer stem cells (LC-SCs) for metastasis may be an effective strategy against lung cancer. This study is the first on epithelial-mesenchymal transition (EMT) properties of boric acid (BA) in LC-SCs. LC-SCs were isolated using the magnetic cell sorting (MACS) method. Tumor-sphere formation and flow cytometry confirmed CSC phenotype. The cytotoxic effect of BA was measured by MTT analysis, and the effect of BA on EMT was examined by migration analysis. The expression levels of ZEB1, SNAIL1, ITGA5, CDH1, ITGB1, VIM, COL1A1, and LAMA5 genes were analyzed by RT-qPCR. E-cadherin, Collagen-1, MMP-3, and Vimentin expressions were analyzed immunohistochemically. Boric acid slightly reduced the migration of cancer cells. Increased expression of transcription factor SNAIL (p < 0.001), but not ZEB1, was observed in LC-SCs. mRNA expression levels of ITGB1 (p < 0.01), ITGA5 (p < 0.001), COL1A1 (p < 0.001), and LAMA5 (p < 0.001) increased; CDH1 and VIM decreased in LC-SCs. Moreover, while E-cadherin (p < 0.001) and Collagen-1 (p < 0.01) immunoreactivities significantly increased, MMP-3 (p < 0.001) and Vimentin (p < 0.01) immunoreactivities decreased in BA-treated LC-SCs. To conclude, the current study provided insights into the efficacy and effects of BA against LC-SCs regarding proliferation, EMT, and cell death for future studies.

Keywords: Boric acid; Cancer stem cell; Cytotoxicity; Epithelial-mesenchymal transition; Lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • AC133 Antigen* / genetics
  • AC133 Antigen* / metabolism
  • Antineoplastic Agents / pharmacology
  • Boric Acids* / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition* / drug effects
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology

Substances

  • Boric Acids
  • AC133 Antigen
  • boric acid
  • PROM1 protein, human
  • Antineoplastic Agents