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Carcinogenesis Advance Access published online on April 19, 2006
Carcinogenesis, doi:10.1093/carcin/bgl044
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received December 19, 2005
Revised March 24, 2006
Accepted March 31, 2006

CARCINOGENESIS

Insubhahibition of proliferation and induction of apoptosis in human breast cancer cells by lauryl gallate

Annarica Calcabrini 1, José Manuel García-Martínez 2, Lorena González 2, Mercedes Julián Tendero 2, María Teresa Agulló Ortuño 2, Pasqualina Crateri 1, Abelardo Lopez-Rivas 2, Giuseppe Arancia 1, Pedro González-Porqué 3, and Jorge Martín-Pérez 2 *

1 Istituto Superiore di Sanità, Rome
2 Instituto de Investigaciones Biomédicas A. Sols (CSIC/UAM), Madrid
3 Servicio de Inmunología, Hospital Ramón y Cajal, Madrid

* To whom correspondence should be addressed.
Jorge Martín-Pérez, E-mail: jmartin{at}iib.uam.es


  Abstract

Lauryl gallate is an antioxidant food additive showing low toxicity to normal cells. Here, its antiproliferative effect has been studied on three human breast cancer cell lines: estrogen-dependent, wild-type p53, MCF7; estrogen-independent, non-functional p53, MDA-MB-231 and MCF7 ADR, which over-expresses P-glycoprotein and displays a multidrug-resistant phenotype. Lauryl gallate inhibited proliferation and induced cell cycle alterations in all three-cell lines without altering P-glycoprotein functionality in the drug-resistant cells. A stable arrest in G1 phase was observed in MCF7, while a slow-down of cell cycle progression was induced in the other two cell lines. Lauryl gallate increased p53 expression only in MCF7, and up-regulated p21Cip1 and reduced cyclin D1 levels in all three-cell lines. The induction of apoptosis, demonstrated by Annexin V-FITC labeling, PARP cleavage, and mitochondrial membrane depolarization and morphological alterations, were clearly detected in MCF7 ADR and MDA-MB-231 and to a minor extent in MCF7. Overexpression of Bcl-2 in MCF7 ADR cells demonstrated its protective role against morphological alterations and apoptosis. Lauryl gallate induction of p21Cip1 and apoptosis observed in all three-cell lines was regulated by Erk1/2 activation. These findings suggest a potential use of lauryl gallate against tumors harboring p53 mutations and drug-resistant phenotypes.

Keywords: lauryl gallate; breast cancer; cell cycle; apoptosis; p-glycoprotein; Bcl-2; Erk1/2; p21Cip1.
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