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A RXR Ligand 6-OH-11-O-Hydroxyphenanthrene with Antitumour Properties Enhances (−)-Epigallocatechin-3-gallate Activity in Three Human Breast Carcinoma Cell Lines
- Source :
- BioMed Research International, BioMed Research International, Vol 2014 (2014)
- Publication Year :
- 2014
- Publisher :
- Hindawi Publishing Corporation, 2014.
-
Abstract
- (−)-Epigallocatechin-3-gallate (EGCG) and chemotherapeutic agents cotreatment can improve cytotoxicity against cancer cells. We showed that EGCG and the rexinoid 6-OH-11-O-hydroxyphenanthrene (IIF), given together, were cytotoxic toward MCF-7, MCF-7TAM, and MDA-MB-231, three breast carcinoma cell lines showing different molecular characteristics. Cell growth arrest and apoptosis were greater after EGCG and IIF cotreatment than after individual administration. Cytotoxicity was related to upregulation of 67-kDa laminin receptor (LR67), one of the principal molecular targets of EGCG, and activation of the nuclear retinoic X receptors (RXRs) pathway. Furthermore, the transcription factor Forkhead box O3 (Foxo3a), a protein able to trigger apoptosis through upregulation of genes necessary for cell death, was activated. EGCG and IIF cotreatment produced a significant nuclear import of Foxo3a from the cytoplasm in MCF-7, MCF-7TAM, and MDA-MB-231 cells. In MCF-7TAM cells only, Foxo3a nuclear localization was associated with p473AKT downregulation. For the first time we showed that when EGCG and IIF, two harmless molecules, were given together, they might increase cytotoxicity in three breast carcinoma cell lines, two of them being representative of poorly responsive breast carcinoma types.
- Subjects :
- Programmed cell death
Article Subject
lcsh:Medicine
Apoptosis
Breast Neoplasms
6-OH-11-O-HYDROXYPHENANTHRENE
Biology
Retinoid X receptor
BREAST CARCINOMA
Ligands
General Biochemistry, Genetics and Molecular Biology
Catechin
Downregulation and upregulation
Antineoplastic Combined Chemotherapy Protocols
Humans
Cytotoxicity
skin and connective tissue diseases
Cell Proliferation
General Immunology and Microbiology
Cell growth
67-kDa LAMININ RECEPTOR
lcsh:R
Forkhead Box Protein O3
food and beverages
Forkhead Transcription Factors
General Medicine
Phenanthrenes
Molecular biology
(–)-EPIGALLOCATECHIN-3-GALLATE (EGCG)
Gene Expression Regulation, Neoplastic
Retinoid X Receptors
Cancer cell
FOXO3
MCF-7 Cells
Female
FOXO3A
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23146141 and 23146133
- Volume :
- 2014
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....abe82d078fdb8b20942b346da4bb6a5b