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


SEMERCİ SEVİMLİ T., SEVİMLİ M., Ghorbani A., ŞAHİNTÜRK V., Qomi Ekenel E., Ertem T., ...More

Naunyn-Schmiedeberg's Archives of Pharmacology, vol.397, no.9, pp.6791-6802, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 397 Issue: 9
  • Publication Date: 2024
  • Doi Number: 10.1007/s00210-024-03062-2
  • Journal Name: Naunyn-Schmiedeberg's Archives of Pharmacology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Veterinary Science Database
  • Page Numbers: pp.6791-6802
  • Keywords: Boric acid, Cancer stem cell, Cytotoxicity, Epithelial-mesenchymal transition, Lung cancer
  • Middle East Technical University Affiliated: Yes

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. Graphical abstract: (Figure presented.)