title: Caffeic acid phenethyl ester activates pro-apoptotic and epithelial-mesenchymal transition-related genes in ovarian cancer cells A2780 and A2780cis.
abstract: Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial-mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy.
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof Dr. Ion Chiricuta", Cluj-Napoca, Romania.|Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gherman
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.|Department of Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.|Department of Surgical Oncology, The Oncological Institute "Prof. Dr. Ion Chiricuta", Cluj-Napoca, Romania.
authors.forename: Ovidiu Leonard
authors.initials: OL
authors.lastname: Braicu
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Zanoaga
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Jurj
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pileczki
authors.affiliation: Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Mahafarin
authors.initials: M
authors.lastname: Maralani
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof Dr. Ion Chiricuta", Cluj-Napoca, Romania.
authors.forename: Flaviu
authors.initials: F
authors.lastname: Drigla
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Braicu
authors.affiliation: Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Liviuta
authors.initials: L
authors.lastname: Budisan
authors.affiliation: Department of Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. pachimas@umfcluj.ro.|Department of Surgical Oncology, The Oncological Institute "Prof. Dr. Ion Chiricuta", Cluj-Napoca, Romania. pachimas@umfcluj.ro.
authors.forename: Patriciu
authors.initials: P
authors.lastname: Achimas-Cadariu
authors.affiliation: Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof Dr. Ion Chiricuta", Cluj-Napoca, Romania. ioana.neagoe@umfcluj.ro.|Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. ioana.neagoe@umfcluj.ro.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
mesh_terms: D017209:Apoptosis; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D002109:Caffeic Acids; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D002945:Cisplatin
keywords: Apoptosis; Caffeic acid phenethyl ester; Epithelial–mesenchymal transition; Ovarian cancer cells
references.citation: Cancer Treat Res. 1994;73:217-48
references.pmid: 7710906
references.citation: Int Immunopharmacol. 2004 Mar;4(3):429-36
references.pmid: 15037220
references.citation: PLoS One. 2014 Jan 22;9(1):e86987
references.pmid: 24466305
references.citation: J Inorg Biochem. 2007 Oct;101(10):1354-61
references.pmid: 17640735
references.citation: Int J Clin Exp Pathol. 2015 Mar 01;8(3):2710-8
references.pmid: 26045776
references.citation: FASEB J. 2006 Oct;20(12):2150-2
references.pmid: 16940438
references.citation: Bioorg Med Chem. 2014 Mar 15;22(6):1809-20
references.pmid: 24565968
references.citation: Toxicology. 2008 Jun 3;248(1):18-24
references.pmid: 18436364
references.citation: Pharmacol Res. 2006 Oct;54(4):293-7
references.pmid: 16887363
references.citation: Int J Oncol. 2012 Sep;41(3):959-68
references.pmid: 22766682
references.citation: Anticancer Res. 2002 Jul-Aug;22(4):2275-80
references.pmid: 12174914
references.citation: Cancer Lett. 2011 Oct 1;309(1):11-8
references.pmid: 21676537
references.citation: Nature. 2002 Dec 19-26;420(6917):860-7
references.pmid: 12490959
references.citation: Exp Toxicol Pathol. 2010 Jan;62(1):45-52
references.pmid: 19268559
references.citation: J Appl Toxicol. 2004 Jan-Feb;24(1):27-35
references.pmid: 14745844
references.citation: Urol Res. 2000 Dec;28(6):360-3
references.pmid: 11221913
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17 ):9090-5
references.pmid: 8799159
references.citation: Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
references.pmid: 24556840
references.citation: Bioorg Med Chem. 2013 Nov 15;21(22):7182-93
references.pmid: 24080105
references.citation: Int J Mol Sci. 2015 May 12;16(5):10748-66
references.pmid: 25984601
references.citation: J Oncol. 2015;2015:865816
references.pmid: 25883654
references.citation: Toxicology. 2006 Jan 16;217(2-3):213-20
references.pmid: 16243424
references.citation: Onco Targets Ther. 2014 Sep 24;7:1663-87
references.pmid: 25285016
references.citation: PLoS One. 2011;6(12 ):e29758
references.pmid: 22242143
references.citation: Fitoterapia. 2002 Nov;73 Suppl 1:S21-9
references.pmid: 12495706
references.citation: Cancer Res. 2003 Mar 15;63(6):1413-9
references.pmid: 12649207
references.citation: J Biol Chem. 1994 Jan 14;269(2):787-90
references.pmid: 8288625
references.citation: Pharmacotherapy. 1996 Jan-Feb;16(1):16-39
references.pmid: 8700790
references.citation: Molecules. 2014 Nov 26;19(12):19610-32
references.pmid: 25432012
references.citation: Cancer Res. 1997 Mar 1;57(5):850-6
references.pmid: 9041185
references.citation: Cancer Causes Control. 2013 May;24(5):989-1004
references.pmid: 23456270
references.citation: Apoptosis. 2015 Apr;20(4):535-50
references.pmid: 25627260
references.citation: Anticancer Drugs. 2006 Aug;17(7):753-62
references.pmid: 16926625
references.citation: Cancer Res. 2013 Aug 15;73(16):5016-28
references.pmid: 23824740
references.citation: Neoplasia. 2008 Sep;10(9):908-19
references.pmid: 18714391
references.citation: J Ovarian Res. 2011 Dec 05;4(1):21
references.pmid: 22141344
references.citation: Cancer Biother Radiopharm. 2012 Mar;27(2):164-8
references.pmid: 22011203