Polysaccharide isolated from persimmon leaves (Diospyros kaki Thunb.) suppresses TGF-β1-induced epithelial-to-mesenchymal transition in A549 cells

Int J Biol Macromol. 2020 Dec 1:164:3835-3845. doi: 10.1016/j.ijbiomac.2020.08.155. Epub 2020 Aug 21.

Abstract

In the present study, to verify the effect of polysaccharides derived from persimmon leaves (PLE) at epithelial-to-mesenchymal transition (EMT), A549 cells were treated with TGF-β1 alone or co-treated with TGF-β1 and PLE (50 and 75 μg/mL). PLE-treated cells showed higher expression of E-cadherin and lower expression of N-cadherin and vimentin compared to TGF-β1-treated cells by inhibiting the levels of transcription factors, including Snail, Slug, and ZEB1, all associated with EMT. PLE also significantly decreased migration, invasion, and anoikis resistance through TGF-β1 mediated EMT suppression, whereby PLE inhibited the levels of MMP-2 and MMP-9 while cleaving PARP. These inhibitory effects of PLE against EMT, migration, invasion, and anoikis resistance were determined by activating the canonical SMAD2/3 and non-canonical ERK/p38 signaling pathways. Therefore, these results suggest that PLE could be used as a potential chemical therapeutic agent for early metastasis of lung cancer in vitro.

Keywords: Epithelial-mesenchymal transition (EMT); Human lung adenocarcinoma cells; Persimmon leaves; Polysaccharide; Transforming growth factor-beta 1 (TGF-β1).

MeSH terms

  • A549 Cells
  • Diospyros / chemistry*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinase 1
  • Plant Leaves / chemistry*
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification*
  • Polysaccharides / pharmacology*
  • Recombinant Proteins
  • Signal Transduction / drug effects
  • Transcription Factors / genetics
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Polysaccharides
  • Recombinant Proteins
  • Transcription Factors
  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 1