PMID- 28465354 OWN - NLM STAT- MEDLINE DCOM- 20180227 LR - 20181202 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 37 IP - 3 DP - 2017 Jun 30 TI - EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion. LID - BSR20170168 [pii] LID - 10.1042/BSR20170168 [doi] AB - 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-gamma (RXRgamma) 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 Tyr(1068) 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. CI - (c) 2017 The Author(s). FAU - Farabegoli, Fulvia AU - Farabegoli F AD - Department of Pharmacology and Biotechnology (FaBiT), University of Bologna, Bologna, Italy fulvia.farabegoli@unibo.it. FAU - Govoni, Marzia AU - Govoni M AD - Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), University of Bologna, Bologna, Italy. FAU - Spisni, Enzo AU - Spisni E AD - Department of Biological, Geological, and Environmental Sciences, (BiGea), University of Bologna, Bologna, Italy. FAU - Papi, Alessio AU - Papi A AD - Department of Biological, Geological, and Environmental Sciences, (BiGea), University of Bologna, Bologna, Italy. LA - eng PT - Journal Article DEP - 20170517 PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (6-OH-11-O-hydroxyphenanthrene) RN - 0 (Phenanthrenes) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 136894-56-9 (Basigin) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Basigin/metabolism MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Catechin/*analogs & derivatives/pharmacology MH - Cell Line, Tumor MH - Cell Movement/*drug effects MH - Down-Regulation/drug effects MH - ErbB Receptors/*antagonists & inhibitors MH - Female MH - Humans MH - MCF-7 Cells MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Neoplasm Invasiveness/*pathology MH - Phenanthrenes/*pharmacology MH - Phosphorylation/drug effects MH - Protein Kinase Inhibitors/pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction/drug effects MH - Tissue Inhibitor of Metalloproteinase-1/metabolism PMC - PMC5434892 OTO - NOTNLM OT - (-)-epigallocatechin-3-gallate (EGCG) OT - 6-OH-11-O-hydroxyphenantrene (IIF) OT - CD44 OT - breast carcinoma OT - epidermal growth factor receptor OT - extracellular matrix metalloproteinase inducer COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2017/05/04 06:00 MHDA- 2018/02/28 06:00 PMCR- 2017/05/17 CRDT- 2017/05/04 06:00 PHST- 2017/02/27 00:00 [received] PHST- 2017/04/27 00:00 [revised] PHST- 2017/05/02 00:00 [accepted] PHST- 2017/05/04 06:00 [pubmed] PHST- 2018/02/28 06:00 [medline] PHST- 2017/05/04 06:00 [entrez] PHST- 2017/05/17 00:00 [pmc-release] AID - BSR20170168 [pii] AID - 10.1042/BSR20170168 [doi] PST - epublish SO - Biosci Rep. 2017 May 17;37(3):BSR20170168. doi: 10.1042/BSR20170168. Print 2017 Jun 30.