Thidiazuron decreases epithelial‐mesenchymal transition activity through the NF‐kB and PI3K/AKT signalling pathways in breast cancer

• Published in: Journal of cellular and molecular medicine 2020-12, Vol.24 (24), p.14525-14538
• Main Authors: Rajendran, Peramaiyan, Ben Ammar, Rebai, Al‐Saeedi, Fatma J., Elsayed Mohamed, Maged, Islam, MIH, Al‐Ramadan, Saeed Y.
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Antibodies; Apoptosis; Biomarkers; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caspase 3 - metabolism; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement; Cell Survival - drug effects; Cell viability; DNA Fragmentation; Epithelial cells; Epithelial-Mesenchymal Transition - drug effects; epithelial‐mesenchymal transition; Female; Gene expression; Growth regulators; Humans; Immunohistochemistry; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Mesenchyme; Metalloproteinase; Metastases; Metastasis; Microscopy; NF-kappa B - metabolism; Original; Penicillin; Phenylurea Compounds - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Poly(ADP-ribose) Polymerases - metabolism; Protein Binding; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signal Transduction - drug effects; Thiadiazoles - pharmacology; Thidiazuron; Tissue inhibitor of metalloproteinases; Toxicity; Transforming growth factor-b; Tumor necrosis factor; Vascular endothelial growth factor; Wound healing
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16079

Breast cancer is the major type among the women population globally. The treatment of cancer metastasis has made modest progress due to multiple factors. Thidiazuron (TDZ) is a novel plant growth regulator that has been shown to have anticancer effects. Therefore, we explored the anti‐metastatic potentials of TDZ in cell lines by assessing its potential to suppress the epithelial‐mesenchymal transition (EMT). We pretreated the BEAS‐2B and breast cancer (MDA‐MB‐231) cells with TDZ and deliberated alteration in a cell viability, mammosphere, migration, NF‐кB signalling, PI3K/AKT signalling and matrix metalloproteinase (MMP) expression and analysed the EMT induction by TGF‐β/TNF‐α‐stimulated BEAS‐2B cells. Treatment with TDZ (5‐50 μmol) diminished the migration and invasion of the extremely metastatic MDA‐MB‐231 cells. Additionally, TDZ treatment led to down‐regulation of uPAR, uPA, VEGF and MMP‐2/‐9 expression and up‐regulation of TIMP‐1/2 expression in these cells. Furthermore, TDZ treatment blocked invasion and EMT in non‐tumorigenic BEAS‐2B epithelial cells stimulated with TGF‐β/TNF‐α.TDZ prevents EMT and may thus block metastasis of breast cancer cells.