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Breast Cancer Research
Published in: Breast Cancer Research 2/2004

Open Access 01-04-2004 | Research article

Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

Authors: Marilena Kampa, Vassilia-Ismini Alexaki, George Notas, Artemissia-Phoebe Nifli, Anastassia Nistikaki, Anastassia Hatzoglou, Efstathia Bakogeorgou, Elena Kouimtzoglou, George Blekas, Dimitrios Boskou, Achille Gravanis, Elias Castanas

Published in: Breast Cancer Research | Issue 2/2004

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Abstract

Introduction

The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid.

Methods

This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production).

Results

The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system.

Conclusions

Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action.
Appendix
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Metadata
Title
Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action
Authors
Marilena Kampa
Vassilia-Ismini Alexaki
George Notas
Artemissia-Phoebe Nifli
Anastassia Nistikaki
Anastassia Hatzoglou
Efstathia Bakogeorgou
Elena Kouimtzoglou
George Blekas
Dimitrios Boskou
Achille Gravanis
Elias Castanas
Publication date
01-04-2004
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2004
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr752

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