EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion.

Abstract

Epidermal growth factor receptor (EGFR) expression is an important marker in breast carcinoma pathology and is considered a pivotal molecule for cancer cell proliferation, invasion and metastasis. We investigated the effects of epigallocatechin-3-gallate (EGCG), the most active green tea catechin, in combination with 6-OH-11-O-hydroxyphenanthrene (IIF), a synthetic retinoid X receptor-γ (RXRγ) agonist, on three breast carcinoma cell lines: MCF-7, MCF-7TAM and MDA-MB-231. EGFR and AKT activation and molecular markers of cell motility and migration (CD44, extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMPs)) were studied after EGCG and IIF treatments. The EGCG + IIF treatment was the most active in down-regulating EGFR phosphorylation at Tyr1068 in all the investigated cell lines; p473AKT was also down-regulated in MCF-TAM cells. EGCG + IIF was also the most active treatment in reducing the expression of markers of invasion and migration in all the three cell lines: CD44, EMMPRIN, MMP-2 and -9 expression decreased, whereas TIMPs were up-regulated. Zymography and scratch assay also confirmed the reduced invasion tendency. We considered that EGCG and IIF treatments could alter the molecular network based on EGFR, CD44 and EMMPRIN expression interdependence and reduced the migration tendency in MCF-7, MCF-7TAM and MDA-MB-231 cells. These events only occurred in association with AKT inactivation in MCF-7TAM cells. In conclusion, the combination of EGCG and IIF significantly attenuated the invasive behaviour of breast carcinoma cells.

• Authors: Fulvia Farabegoli, Marzia Govoni, Enzo Spisni, Alessio Papi
• Journal: Bioscience reports (Biosci Rep) Vol. 37 Issue 3 (Jun 30 2017) ISSN: 1573-4935 [Electronic] England
• PMID: 28465354 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s).

Chemical References

• 6-OH-11-O-hydroxyphenanthrene
• Phenanthrenes
• Protein Kinase Inhibitors
• Tissue Inhibitor of Metalloproteinase-1
• Basigin
• Catechin
• epigallocatechin gallate
• EGFR protein, human
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Basigin (metabolism)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Catechin (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Down-Regulation (drug effects)
• ErbB Receptors (antagonists & inhibitors)
• Female
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Invasiveness (pathology)
• Phenanthrenes (pharmacology)
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)