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Nutritional flavonoids modulate estrogen receptor alpha signaling
Fabio Virgili1, Filippo Acconcia, Roberto Ambra
1Department of Biology, University Roma Tre, Viale G. Marconi, 446, I-00146 Rome, Italy.
IUBMB Life
|June 10, 2004
Summary
Flavonoids like naringenin and quercetin mimic estrogen receptor alpha (ERalpha) transcriptional activity but block rapid signaling pathways. This decoupling of ERalpha signaling may explain their protective effects against estrogen-driven cancers.
Area of Science:
- Molecular Endocrinology
- Cancer Biology
- Nutritional Biochemistry
Background:
- Estrogen receptor alpha (ERalpha) mediates 17beta-estradiol (E2) effects via gene transcription and rapid non-genomic signaling, implicated in E2-related cancers.
- Nutritional flavonoids possess anticancer properties, potentially through antioxidant or kinase-altering mechanisms, but their antiestrogenic effects and precise antitumoral mechanisms remain unclear.
Purpose of the Study:
- To investigate if flavonoids' antimitogenic effects are mediated by modulating ERalpha-mediated rapid signaling.
- To characterize the impact of naringenin and quercetin on ERalpha activity and signaling pathways in cancer cells.
Main Methods:
- Transiently transfected HeLa cells (ERalpha-negative) with a human ERalpha expression vector to render them E2-sensitive.
- Studied the ability of naringenin and quercetin, compared to E2, to induce ERalpha transcriptional activity and modulate rapid signaling pathways (e.g., MAPK/ERK).
Main Results:
- Flavonoids (naringenin, quercetin) acted as E2 mimetics on ERalpha transcriptional activity.
- Flavonoids impaired the activation of rapid signaling pathways crucial for E2-induced proliferation.
Conclusions:
- Flavonoids can decouple ERalpha signal transduction by mimicking transcriptional activity while inhibiting rapid signaling.
- This decoupling mechanism offers a novel explanation for the protective and anticarcinogenic effects of flavonoids against E2-related cancers.