title: Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces apoptosis in human breast cancer cells.
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.
authors.affiliation: 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.
authors.forename: Lamia
authors.initials: L
authors.lastname: Hamdan
authors.forename: Zoheir
authors.initials: Z
authors.lastname: Arrar
authors.forename: Yacoub
authors.initials: Y
authors.lastname: Al Muataz
authors.forename: Lutfi
authors.initials: L
authors.lastname: Suleiman
authors.forename: Claude
authors.initials: C
authors.lastname: Négrier
authors.forename: Joseph Kajima
authors.initials: JK
authors.lastname: Mulengi
authors.forename: Habib
authors.initials: H
authors.lastname: Boukerche
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C029010:cinnamic acid
references.citation: Cancer Res. 2000 Oct 15;60(20):5848-56
references.pmid: 11059782
references.citation: Biochem J. 1976 Feb 15;154(2):405-14
references.pmid: 7237
references.citation: Cell Growth Differ. 1995 Nov;6(11):1395-403
references.pmid: 8562478
references.citation: Biochem J. 2012 Jun 15;444(3):561-71
references.pmid: 22458763
references.citation: Apoptosis. 1999 Feb;4(1):39-45
references.pmid: 14634294
references.citation: Neurosci Res. 2004 Jan;48(1):13-20
references.pmid: 14687877
references.citation: Cancer Res. 2005 Dec 1;65(23):10901-11
references.pmid: 16322237
references.citation: Mol Cancer Ther. 2003 Apr;2(4):383-8
references.pmid: 12700282
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Biochem Biophys Res Commun. 2003 May 9;304(3):437-44
references.pmid: 12729577
references.citation: PLoS One. 2011;6(7):e22429
references.pmid: 21799851
references.citation: Breast Cancer Res. 2008;10(1):202
references.pmid: 18304378
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18131-6
references.pmid: 19826085
references.citation: Physiol Behav. 2004 Jan;80(4):489-98
references.pmid: 14741234
references.citation: Neoplasia. 2011 Jul;13(7):620-32
references.pmid: 21750656
references.citation: BJU Int. 2012 Oct;110(7):1062-9
references.pmid: 22394625
references.citation: Genes Dev. 1996 Feb 15;10(4):461-77
references.pmid: 8600029
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9679-83
references.pmid: 9275183
references.citation: J Clin Invest. 2008 Dec;118(12):3930-42
references.pmid: 19033663
references.citation: Neurosurgery. 2006 Dec;59(6):1313-23; discussion 1323-4
references.pmid: 17277695
references.citation: Anticancer Res. 2006 Sep-Oct;26(5A):3561-6
references.pmid: 17094483
references.citation: J Bioenerg Biomembr. 2012 Feb;44(1):127-39
references.pmid: 22407107
references.citation: Nat Rev Cancer. 2011 Feb;11(2):85-95
references.pmid: 21258394
references.citation: Genomics. 2004 Dec;84(6):1014-20
references.pmid: 15533718
references.citation: IUBMB Life. 2012 Jan;64(1):1-9
references.pmid: 22131303
references.citation: Biochem J. 2010 Jan 27;426(1):31-41
references.pmid: 19916962
references.citation: Nat Med. 2001 May;7(5):548-52
references.pmid: 11329054
references.citation: Curr Opin Cell Biol. 2003 Dec;15(6):691-9
references.pmid: 14644193
references.citation: Endocr Relat Cancer. 2006 Jun;13(2):293-325
references.pmid: 16728565
references.citation: Carcinogenesis. 2001 Oct;22(10):1607-14
references.pmid: 11576999
references.citation: Adv Drug Deliv Rev. 2007 Jul 10;59(6):491-504
references.pmid: 17532091
references.citation: Cancer. 2008 Oct 15;113(8 Suppl):2221-43
references.pmid: 18816619
references.citation: Glia. 2005 Dec;52(4):276-88
references.pmid: 16001426
references.citation: Mol Cancer Ther. 2003 Feb;2(2):165-71
references.pmid: 12589033
references.citation: J Mol Med (Berl). 2011 Mar;89(3):205-12
references.pmid: 21301795