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

• Published in: PloS one Vol. 8; no. 9; p. e72953
• Main Authors: Hamdan, Lamia, Arrar, Zoheir, Al Muataz, Yacoub, Suleiman, Lutfi, Négrier, Claude, Mulengi, Joseph Kajima, Boukerche, Habib
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.09.2013; Public Library of Science (PLoS)
• Subjects: Acids; Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; BAX protein; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer therapies; Cancer treatment; Cell death; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cinnamates - administration & dosage; Cinnamates - chemistry; Cinnamates - pharmacology; Comparative analysis; Cytotoxicity; Defects; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial cells; Female; Humans; Life Sciences; MCF-7 Cells; Melanoma; Metabolism; Metastasis; Neoplastic Stem Cells - drug effects; Nitriles; p53 Protein; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Time Factors; Tumor Burden - drug effects; Tumor cells; Tumor proteins; Tumor Stem Cell Assay; Tumor suppressor genes; Tumors; Viability; Xenograft Model Antitumor Assays; France; Cancer treatment; Epithelial cells; Breast cancer; Cell staining; Cell immortalization; Prostate cancer; MTT assay; Apoptosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0072953

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.