The phytoestrogens daidzein and equol inhibit the drug transporter BCRP/ABCG2 in breast cancer cells: potential chemosensitizing effect
Purpose: The soy isoflavone genistein has been described to up-regulate breast cancer resistance protein (BCRP) and, thus, enhance chemoresistance in breast cancer cells. The aim of this work was to assess the effect of long- and short-term incubation with daidzein, the second most abundant soy isof...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
European journal of nutrition
Year: 2019, Volume: 58, Issue: 1, Pages: 139-150 |
| ISSN: | 1436-6215 |
| DOI: | 10.1007/s00394-017-1578-9 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1007/s00394-017-1578-9 Verlag, Volltext: https://link.springer.com/article/10.1007/s00394-017-1578-9 
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| Author Notes: | Juan Pablo Rigalli, Paul Niklas Scholz, Guillermo Nicolás Tocchetti, María Laura Ruiz, Johanna Weiss |
MARC
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| 245 | 1 | 4 | |a The phytoestrogens daidzein and equol inhibit the drug transporter BCRP/ABCG2 in breast cancer cells |b potential chemosensitizing effect |c Juan Pablo Rigalli, Paul Niklas Scholz, Guillermo Nicolás Tocchetti, María Laura Ruiz, Johanna Weiss |
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| 520 | |a Purpose: The soy isoflavone genistein has been described to up-regulate breast cancer resistance protein (BCRP) and, thus, enhance chemoresistance in breast cancer cells. The aim of this work was to assess the effect of long- and short-term incubation with daidzein, the second most abundant soy isoflavone and its metabolite equol on the expression and activity of P-glycoprotein, multidrug resistance-associated proteins 1 and 2 (MRP1 and MRP2) and BCRP in breast cancer cells. Methods: MCF-7 and MDA-MB-231 cells were treated with phytoestrogen concentrations within the range achieved in individuals with a high isoflavone intake. Transporter expression was evaluated at protein and mRNA level through western blot and qRT-PCR, respectively. Transporter activity was determined using doxorubicin, mitoxantrone and carboxy-dichlorofluorescein as substrates. Results: Daidzein (5 µM) up-regulated MRP2- and down-regulated MRP1 protein expressions in MCF-7 and MDA-MB-231 cells, respectively. Both effects were ER-dependent, as determined using the antagonist ICI 182,780. The decrease in MRP1 mRNA in MDA-MB-231 cells indicates a transcriptional mechanism. On the contrary, MRP2 induction in MCF-7 cells takes place post-transcriptionally. Whereas changes in the transporter expression had a minor effect on the transporter activity, acute incubation with daidzein, R-equol and S-equol led to a strong inhibition of BCRP activity and an increase in the IC50 of BCRP substrates. Conclusions: In contrast to previous reports for genistein, daidzein and equol do not provoke a major up-regulation of the transporter expression but instead an inhibition of BCRP activity and sensitization to BCRP substrates. | ||
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| 700 | 1 | |a Tocchetti, Guillermo Nicolás |e VerfasserIn |0 (DE-588)1161690220 |0 (DE-627)1025156013 |0 (DE-576)506811190 |4 aut | |
| 700 | 1 | |a Weiß, Johanna |e VerfasserIn |0 (DE-588)1050230906 |0 (DE-627)783666322 |0 (DE-576)404441114 |4 aut | |
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