PMID- 26278714 OWN - NLM STAT- MEDLINE DCOM- 20161228 LR - 20191027 IS - 1873-5576 (Electronic) IS - 1568-0096 (Linking) VI - 16 IP - 4 DP - 2016 TI - Epigallocatechin-3-gallate Increases RXRgamma-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines. PG - 373-85 AB - Molecules with synergistic effects often enhance the benefits of cancer therapy. We observed that the major catechin of green tea, (-)-Epigallocatechin-3-gallate (EGCG), induced retinoid X receptor-gamma (RXRgamma) expression in the SK-Ch-A1 cholangiocarcinoma cell line and in two colon carcinoma cell lines (LoVo and the derivative multi-drug resistant LoVoMDR). On this basis, we analyzed the effects of EGCG in combination with an RXRgamma ligand, 6-OH-11-O-hydroxyphenantrene (IIF), or with a ligand of retinoic acid receptor, all-trans-retinoic acid (RA). IIF alone and in combination with EGCG activated the retinoic X response elements and induced the germ cell nuclear factor. In parallel, EGCG induced 67 kDa laminin receptor expression alone and in combination with IIF. We observed a synergistic growth inhibition with EGCG and IIF in combination at lower doses. These effects were accompanied by apoptosis activation through the mitochondrial pathway. Moreover, in LoVo cell line we observed an induction of Forkhead box O3 expression, another molecule involved in apoptosis activation. Finally, metalloproteinase activity and extracellular matrix metalloproteinase inducer (EMMPRIN) expression were inhibited and tumor cell invasion was strongly reduced in the SK-Ch-A1 cell line after treatment with EGCG and IIF. In conclusion, the use of specific RXR ligands in combination with catechins could open a new perspective in gastrointestinal tumor chemoprevention. FAU - Papi, Alessio AU - Papi A AD - Department of Biological, Geological, and Environmental Science (BiGea), Via Selmi 3, University of Bologna, 40126 Bologna, Italy. alessio.papi2@unibo.it. FAU - Govoni, Marzia AU - Govoni M FAU - Ciavarella, Carmen AU - Ciavarella C FAU - Spisni, Enzo AU - Spisni E FAU - Orlandi, Marina AU - Orlandi M FAU - Farabegoli, Fulvia AU - Farabegoli F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Curr Cancer Drug Targets JT - Current cancer drug targets JID - 101094211 RN - 0 (6-OH-11-O-hydroxyphenanthrene) RN - 0 (Forkhead Box Protein O3) RN - 0 (Ligands) RN - 0 (Phenanthrenes) RN - 0 (Retinoid X Receptor gamma) RN - 0 (Tea) RN - 5688UTC01R (Tretinoin) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 3.4.- (Metalloproteases) SB - IM MH - Apoptosis/*drug effects MH - Catechin/*analogs & derivatives/pharmacology MH - Cell Line, Tumor MH - Drug Synergism MH - Forkhead Box Protein O3/metabolism MH - Gastrointestinal Neoplasms/*drug therapy/metabolism MH - Humans MH - Ligands MH - Metalloproteases/metabolism MH - Mitochondria/drug effects/metabolism MH - Phenanthrenes/*pharmacology MH - Retinoid X Receptor gamma/*metabolism MH - Tea/metabolism MH - Tretinoin/metabolism EDAT- 2015/08/19 06:00 MHDA- 2016/12/29 06:00 CRDT- 2015/08/18 06:00 PHST- 2015/03/24 00:00 [received] PHST- 2015/07/21 00:00 [revised] PHST- 2015/08/13 00:00 [accepted] PHST- 2015/08/18 06:00 [entrez] PHST- 2015/08/19 06:00 [pubmed] PHST- 2016/12/29 06:00 [medline] AID - CCDT-EPUB-69573 [pii] AID - 10.2174/1568009615666150817120931 [doi] PST - ppublish SO - Curr Cancer Drug Targets. 2016;16(4):373-85. doi: 10.2174/1568009615666150817120931.