Approaches in Hydroxytyrosol Supplementation on Epithelial—Mesenchymal Transition in TGFβ1-Induced Human Respiratory Epithelial Cells

Abstract

Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial–mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose–response study and growth kinetic study on RECs was performed. Several approaches on HT treatment and TGFβ1 induction with varying durations and methods was studied. RECs morphology and migration ability were evaluated. Vimentin and E-cadherin immunofluorescence staining and Western blotting [E-cadherin, vimentin, SNAIL/SLUG, AKT, phosphorylated (p)AKT, SMAD2/3 and pSMAD2/3] were performed after 72-h treatment. In silico analysis (molecular docking) of HT was performed to evaluate the potential of HT to bind with the TGFβ receptor. The viability of the HT-treated RECs was concentration-dependent, where the median effective concentration (EC50) was 19.04 μg/mL. Testing of the effects of 1 and 10 µg/mL HT revealed that HT suppressed expression of the protein markers vimentin and SNAIL/SLUG while preserving E-cadherin protein expression. Supplementation with HT protected against SMAD and AKT pathway activation in the TGFβ1-induced RECs. Furthermore, HT demonstrated the potential to bind with ALK5 (a TGFβ receptor component) in comparison to oleuropein. TGFβ1-induced EMT in RECs and HT exerted a positive effect in modulating the effects of EMT.

Hydroxytyrosol Alleviates Methotrexate-Induced Pulmonary Fibrosis in Rats: Involvement of TGF-β1, Tissue Factor, and VEGF

“…In line with these positive results, MTX treatment has improved histopathological scores in a dose-dependent pattern. These data are aligned with Razali et al, 31) who stated that HT has provided protection against SMAD and AKT pathway activation in the TGFβ1-induced epithelial-mesenchymal transition (EMT) respiratory epithelial cells (RECs).…”

An Antibody of the Secreted Isoform of Disintegrin and Metalloprotease 9 (sADAM9) Inhibits Epithelial–Mesenchymal Transition and Migration of Prostate Cancer Cell Lines

“…EMT is a phenomenon in which epithelial cells are converted into motile mesenchymal cells [ 27 ], and we investigated EMT as the main phenomenon causing cell migration and invasion. Slug is one of the EMT inducers; E-cadherin is a marker of epithelial cells; and N-cadherin and Vimentin are markers of mesenchymal cells [ 28 , 29 ]. When EMT is suppressed, the expression of E-cadherin increases while that of Slug, N-cadherin, and Vimentin decreases.…”

Role of Olive Bioactive Compounds in Respiratory Diseases

“…The c-MET inhibitors showed promising results in lung cancer prevention in both animal models and clinical trials [ 175 , 176 ]. Hydroxytyrosol was also reported to have reversed TGFβ1-induced EMT in respiratory epithelial cells by inhibiting AKT and SMAD2/3 expression [ 177 ]. Thus, hydroxytyrosol could be exploited for cancer prevention by targeting c-MET inhibition.…”