title: Cytotoxicity of cyclodipeptides from Pseudomonas aeruginosa PAO1 leads to apoptosis in human cancer cell lines.
abstract: Pseudomonas aeruginosa is an opportunistic pathogen of plants and animals, which produces virulence factors in order to infect or colonize its eukaryotic hosts. Cyclodipeptides (CDPs) produced by P. aeruginosa exhibit cytotoxic properties toward human tumor cells. In this study, we evaluated the effect of a CDP mix, comprised of cyclo(L-Pro-L-Tyr), cyclo(L-Pro-L-Val), and cyclo(L-Pro-L-Phe) that were isolated from P. aeruginosa, on two human cancer cell lines. Our results demonstrated that the CDP mix promoted cell death in cultures of the HeLa cervical adenocarcinoma and Caco-2 colorectal adenocarcinoma cell lines in a dose-dependent manner, with a 50% inhibitory concentration (IC50) of 0.53 and 0.66 mg/mL, for HeLa and Caco-2 cells, respectively. Flow cytometric analysis, using annexin V and propidium iodide as apoptosis and necrosis indicators, respectively, clearly showed that HeLa and Caco-2 cells exhibited apoptotic characteristics when treated with the CDP mix at a concentration <0.001 mg/mL. IC50 values for apoptotic cells in HeLa and Caco-2 cells were 6.5 × 10(-5) and 1.8 × 10(-4) mg/mL, respectively. Our results indicate that an apoptotic pathway is involved in the inhibition of cell proliferation caused by the P. aeruginosa CDP mix.
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: Dolores
authors.initials: D
authors.lastname: Vázquez-Rivera
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: Omar
authors.initials: O
authors.lastname: González
authors.affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootécnia, UMSNH, 58893 Morelia, MICH, Mexico.
authors.forename: Jaquelina
authors.initials: J
authors.lastname: Guzmán-Rodríguez
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: Alma L
authors.initials: AL
authors.lastname: Díaz-Pérez
authors.affiliation: Centro Multidisciplinario de Estudios en Biotecnología, Facultad de Medicina Veterinaria y Zootécnia, UMSNH, 58893 Morelia, MICH, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ochoa-Zarzosa
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: López-Bucio
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: Víctor
authors.initials: V
authors.lastname: Meza-Carmen
authors.affiliation: Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Edificio B-3, Ciudad Universitaria, 58030 Morelia, MICH, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Campos-García
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000145:classification* / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides
references.citation: Chem Biol. 2002 Dec;9(12):1355-64
references.pmid: 12498889
references.citation: Appl Environ Microbiol. 2002 Sep;68(9):4322-7
references.pmid: 12200282
references.citation: PLoS One. 2008;3(2):e1619
references.pmid: 18286176
references.citation: Curr Clin Pharmacol. 2013 Aug;8(3):247-55
references.pmid: 23343017
references.citation: Bioorg Med Chem. 2012 Mar 15;20(6):2002-9
references.pmid: 22356736
references.citation: J Bacteriol. 2008 Nov;190(21):7130-40
references.pmid: 18757543
references.citation: Nature. 2000 Aug 31;406(6799):959-64
references.pmid: 10984043
references.citation: Curr Microbiol. 2002 Oct;45(4):250-4
references.pmid: 12192521
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16948-52
references.pmid: 17075036
references.citation: Chem Sci. 2013 Apr 1;4(4):1646-1657
references.pmid: 23914293
references.citation: Anticancer Res. 2004 May-Jun;24(3a):1713-9
references.pmid: 15274345
references.citation: Biomed Res Int. 2014;2014:126586
references.pmid: 24527434
references.citation: Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7253-8
references.pmid: 21482761
references.citation: J Microbiol Biotechnol. 2008 Apr;18(4):682-5
references.pmid: 18467861
references.citation: Chem Biol. 2011 Nov 23;18(11):1362-8
references.pmid: 22118670
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):3912-7
references.pmid: 21325056
references.citation: Science. 2010 Jul 16;329(5989):294-6
references.pmid: 20522739
references.citation: ACS Chem Biol. 2009 Dec 18;4(12):1051-9
references.pmid: 19928886
references.citation: Microbiol Mol Biol Rev. 2006 Dec;70(4):859-75
references.pmid: 17158701
references.citation: Biofouling. 2006;22(3-4):201-8
references.pmid: 17290864
references.citation: Front Chem. 2014 May 01;2:20
references.pmid: 24822174
references.citation: J Bacteriol. 2006 Mar;188(6):2214-21
references.pmid: 16513751
references.citation: BMC Microbiol. 2014;14:118
references.pmid: 24885173
references.citation: Annu Rev Microbiol. 2001;55:165-99
references.pmid: 11544353
references.citation: Curr Med Chem. 2012;19(21):3564-77
references.pmid: 22709011
references.citation: Mol Microbiol. 1999 Sep;33(6):1254-66
references.pmid: 10510239
references.citation: J Pept Sci. 2014 Mar;20(3):173-85
references.pmid: 24353056
references.citation: J Microbiol. 2013 Dec;51(6):836-43
references.pmid: 24385362