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European Journal of Nutrition

Erschienen in:

01.06.2012 | Original Contribution

CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract

verfasst von: Carlota Oleaga, Miriam García, Anna Solé, Carlos J. Ciudad, Maria Izquierdo-Pulido, Véronique Noé

Erschienen in: European Journal of Nutrition | Ausgabe 4/2012

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Abstract

Purpose

To evaluate the effect of cocoa flavonoids in breast cancer cells at the molecular level, a functional genomic analysis was performed using a polyphenolic cocoa extract (PCE) in MCF-7 and SKBR3 cell lines.

Methods

The expression profile of 84 genes included in the Stress & Toxicity PathwayFinder™ PCR Array was analyzed after PCE incubation for 24 h. mRNA and protein levels were analyzed by RT-PCR and western blot, respectively. Gel shift assays were used to evaluate DNA–protein complexes. Protein complexes were identified by co-immunoprecipitation. Cell viability was evaluated by MTT assays.

Results

Upon PCE incubation, 7 genes were overexpressed and 1 underexpressed in MCF-7 cells, whereas 9 genes were overexpressed in SKBR3 cells. Among the differentially expressed genes in both cell lines, cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) was chosen for further study. CYP1A1 mRNA and protein levels and enzymatic activity increased upon PCE incubation. CYP1A1 transcriptional activation by PCE was mediated through AhR binding to XRE elements within the CYP1A1 promoter in MCF-7 cells. A protein complex including AhR and ERα was detected. The combination of PCE with tamoxifen caused a synergistic cytotoxicity in both cell lines and was due to an increase in apoptosis in MCF-7 cells.

Conclusions

The interaction between ERα and AhR upon incubation with PCE leads to CYP1A1 induction in breast cancer cells. The synergy between PCE and non-cytotoxic tamoxifen concentrations opens the possibility for a combination therapy based on polyphenols from cocoa that increased tamoxifen efficacy.

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Titel: CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract
verfasst von: Carlota Oleaga
Miriam García
Anna Solé
Carlos J. Ciudad
Maria Izquierdo-Pulido
Véronique Noé
Publikationsdatum: 01.06.2012
Verlag: Springer-Verlag
Erschienen in: European Journal of Nutrition / Ausgabe 4/2012
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-011-0231-2

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CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract