Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells

Lamia Hamdan; Zoheir Arrar; Yacoub Al Muataz; Lutfi Suleiman; Claude Négrier; Joseph Kajima Mulengi; Habib Boukerche

doi:10.1371/journal.pone.0072953

Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells

PLoS One. 2013 Sep 5;8(9):e72953. doi: 10.1371/journal.pone.0072953. eCollection 2013.

Authors

Lamia Hamdan¹, Zoheir Arrar, Yacoub Al Muataz, Lutfi Suleiman, Claude Négrier, Joseph Kajima Mulengi, Habib Boukerche

Affiliation

¹ Unité de Recherche Mixte EA4174, Université Claude Bernard Lyon1, INSERM, Lyon, France ; Department de Chimie Organique, Substances Naturelles et Analyses, University de Tlemcen, Tlemcen, Algerie.

Abstract

This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial cells, and compared their cytotoxic effects responses. Treatment of breast cancer cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent decrease of cell proliferation, viability in colony formation assay, and programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The ability of ACCA to suppress growth in cancer cells not expressing or containing defects in p53 gene indicates a lack of involvement of this critical tumor suppressor element in mediating ACCA-induced growth inhibition. Induction of apoptosis correlated with an increase in Bax protein, an established inducer of programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of apoptosis. We also documented the ability of ACCA to inhibit the migration and invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA-231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis of its selective anticancer inhibitory activity on tumor cells, ACCA may represent a promising therapeutic drug that should be further evaluated as a chemotherapeutic agent for human breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cinnamates / administration & dosage
Cinnamates / chemistry
Cinnamates / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Humans
MCF-7 Cells
Neoplastic Stem Cells / drug effects
Proto-Oncogene Proteins c-bcl-2 / metabolism
Time Factors
Tumor Burden / drug effects
Tumor Stem Cell Assay
Xenograft Model Antitumor Assays
bcl-2-Associated X Protein / metabolism

Substances

Antineoplastic Agents
Cinnamates
Proto-Oncogene Proteins c-bcl-2
bcl-2-Associated X Protein
cinnamic acid

Grants and funding

This was supported by grants from the General Directorate for Scientific Research and Technological Development (GDSR Ministry of Higher Education and Scientific Research/Algeria), and the Ligue nationale contre le Cancer. LH was supported by a salary support from GSDR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.