{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T09:55:06Z","timestamp":1772186106719,"version":"3.50.1"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T00:00:00Z","timestamp":1360713600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0055651","type":"journal-article","created":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T17:08:58Z","timestamp":1360775338000},"page":"e55651","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Norspermidine and Novel Pd(II) and Pt(II) Polynuclear Complexes of Norspermidine as Potential Antineoplastic Agents Against Breast Cancer"],"prefix":"10.1371","volume":"8","author":[{"given":"T\u00e2nia Magalh\u00e3es","family":"Silva","sequence":"first","affiliation":[]},{"given":"Sara","family":"Andersson","sequence":"additional","affiliation":[]},{"given":"Sunil Kumar","family":"Sukumaran","sequence":"additional","affiliation":[]},{"given":"Maria Paula","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Lo","family":"Persson","sequence":"additional","affiliation":[]},{"given":"Stina","family":"Oredsson","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,2,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1177\/153537020322800903","article-title":"Apoptosis, chemoresistance, and breast cancer: insights from the MCF-7 cell model system","volume":"228","author":"R Simstein","year":"2003","journal-title":"Exp Biol Med (Maywood)"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1677\/erc.0.0060069","article-title":"Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment","volume":"6","author":"NE Davidson","year":"1999","journal-title":"Endocr Relat Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.clon.2005.04.001","article-title":"Platinum-based chemotherapy in metastatic breast cancer: the Leicester (U.K.) experience","volume":"17","author":"MP Decatris","year":"2005","journal-title":"Clin Oncol (R Coll Radiol)"},{"key":"ref4","first-page":"759","article-title":"Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy","volume":"48","author":"AE Pegg","year":"1988","journal-title":"Cancer Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"4551","DOI":"10.1021\/jm900187v","article-title":"Recent advances in the development of polyamine analogues as antitumor agents","volume":"52","author":"RA Casero Jr","year":"2009","journal-title":"J Med Chem"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s00726-009-0396-7","article-title":"Polyamines: fundamental characters in chemistry and biology","volume":"38","author":"E Agostinelli","year":"2010","journal-title":"Amino Acids"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20031327","article-title":"A perspective of polyamine metabolism","volume":"376","author":"HM Wallace","year":"2003","journal-title":"Biochem J"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.biocel.2005.10.020","article-title":"Induction of apoptotic cell death by putrescine","volume":"38","author":"K Takao","year":"2006","journal-title":"Int J Biochem Cell Biol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cccn.2004.02.022","article-title":"Polyamines as clinical laboratory tools","volume":"344","author":"A Gugliucci","year":"2004","journal-title":"Clin Chim Acta"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrc1454","article-title":"Polyamines and cancer: old molecules, new understanding","volume":"4","author":"EW Gerner","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/bst0310393","article-title":"Polyamine analogues as anticancer drugs","volume":"31","author":"HM Wallace","year":"2003","journal-title":"Biochem Soc Trans"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00726-007-0534-z","article-title":"Polyamine analogues - an update","volume":"33","author":"HM Wallace","year":"2007","journal-title":"Amino Acids"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1096\/fj.09-135889","article-title":"Caenorhabditis elegans P5B-type ATPase CATP-5 operates in polyamine transport and is crucial for norspermidine-mediated suppression of RNA interference","volume":"24","author":"A Heinick","year":"2010","journal-title":"FASEB J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pharmthera.2005.02.001","article-title":"Pharmacological aspects of cytotoxic polyamine analogs and derivatives for cancer therapy","volume":"107","author":"N Seiler","year":"2005","journal-title":"Pharmacol Ther"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2174\/157018011797655197","article-title":"MGBG in Combined Anticancer Chemotherapy","volume":"8","author":"RF Gonsalves","year":"2011","journal-title":"Lett Drug Des Discov"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.tox.2006.03.009","article-title":"Differential polyamine analogue effects in four human breast cancer cell lines","volume":"223","author":"CM Holst","year":"2006","journal-title":"Toxicology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/CAD.0b013e3282f7f518","article-title":"Different cell cycle kinetic effects of N1,N11-diethylnorspermine-induced polyamine depletion in four human breast cancer cell lines","volume":"19","author":"L Myhre","year":"2008","journal-title":"Anticancer Drugs"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/jm000084m","article-title":"Terminally alkylated polyamine analogues as chemotherapeutic agents","volume":"44","author":"RA Casero Jr","year":"2001","journal-title":"J Med Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1097\/CAD.0b013e32830f902b","article-title":"Molecular mechanisms underlying N1, N11-diethylnorspermine-induced apoptosis in a human breast cancer cell line","volume":"19","author":"CM Holst","year":"2008","journal-title":"Anticancer Drugs"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0027-5107(96)00020-6","article-title":"DNA adducts from chemotherapeutic agents","volume":"355","author":"PD Lawley","year":"1996","journal-title":"Mutat Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrd1691","article-title":"Cellular processing of platinum anticancer drugs","volume":"4","author":"D Wang","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/S0959-8049(98)00224-X","article-title":"Clinical development of platinum complexes in cancer therapy: an historical perspective and an update","volume":"34","author":"D Lebwohl","year":"1998","journal-title":"Eur J Cancer"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"185104","DOI":"10.1063\/1.2787528","article-title":"Conformational and vibrational study of platinum(II) anticancer drugs: cis-diamminedichloro-platinum(II) as a case study","volume":"127","author":"AM Amado","year":"2007","journal-title":"J Chem Phys"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/cphc.201001067","article-title":"Inelastic neutron scattering study of Pt(II) complexes displaying anticancer properties","volume":"12","author":"LA de Carvalho","year":"2011","journal-title":"Chemphyschem"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinorgbio.2011.11.021","article-title":"Novel Pt(II) and Pd(II) complexes with polyamine analogues: synthesis and vibrational analysis","volume":"108","author":"TM Silva","year":"2012","journal-title":"J Inorg Biochem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0167-4889(01)00186-0","article-title":"Cytotoxic effects of metal complexes of biogenic polyamines. I. Platinum(II) spermidine compounds: prediction of their antitumour activity","volume":"1589","author":"MP Marques","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1021\/jm0311238","article-title":"Cytotoxic activity of metal complexes of biogenic polyamines: polynuclear platinum(II) chelates","volume":"47","author":"LJ Teixeira","year":"2004","journal-title":"J Med Chem"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2174\/157018006776286989","article-title":"Pt(II) vs Pd(II) polyamine complexes as new anticancer drugs: A structure-activity study","volume":"3","author":"SM Fiuza","year":"2006","journal-title":"Lett Drug Des Discov"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1747-0285.2011.01081.x","article-title":"Biologic activity of a dinuclear Pd(II)-spermine complex toward human breast cancer","volume":"77","author":"SM Fiuza","year":"2011","journal-title":"Chem Biol Drug Des"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ejmech.2011.12.001","article-title":"Antiproliferative effect of novel platinum(II) and palladium(II) complexes on hepatic tumor stem cells in vitro","volume":"49","author":"N Miklasova","year":"2012","journal-title":"Eur J Med Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/oxfordjournals.jbchem.a133818","article-title":"Widespread occurrence of norspermidine and norspermine in eukaryotic algae","volume":"91","author":"K Hamana","year":"1982","journal-title":"J Biochem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1104\/pp.89.2.525","article-title":"Detection of Norspermidine and Norspermine in Medicago sativa L. (Alfalfa)","volume":"89","author":"B Rodriguez-Garay","year":"1989","journal-title":"Plant Physiol"},{"key":"ref33","first-page":"563","article-title":"Antitumor activity of norspermidine, a structural homologue of the natural polyamine spermidine","volume":"8","author":"NJ Prakash","year":"1988","journal-title":"Anticancer Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1021\/jm960849j","article-title":"A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics","volume":"40","author":"RJ Bergeron","year":"1997","journal-title":"J Med Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.tiv.2004.10.005","article-title":"Comparison of three cytotoxicity tests in the evaluation of the cytotoxicity of a spermine analogue on human breast cancer cell lines","volume":"19","author":"CM Holst","year":"2005","journal-title":"Toxicol In Vitro"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1006\/abbi.1993.1311","article-title":"Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction","volume":"303","author":"MV Berridge","year":"1993","journal-title":"Arch Biochem Biophys"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.yexcr.2005.04.027","article-title":"Importance of polyamines in cell cycle kinetics as studied in a transgenic system","volume":"308","author":"S Nasizadeh","year":"2005","journal-title":"Exp Cell Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1365-2184.1996.tb00988.x","article-title":"Normal G1\/S transition and prolonged S phase within one cell cycle after seeding cells in the presence of an ornithine decarboxylase inhibitor","volume":"29","author":"JO Fredlund","year":"1996","journal-title":"Cell Prolif"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/cyto.990060618","article-title":"A method to measure the duration of DNA synthesis and the potential doubling time from a single sample","volume":"6","author":"AC Begg","year":"1985","journal-title":"Cytometry"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2184.1994.tb01422.x","article-title":"Abnormal DNA synthesis in polyamine deficient cells revealed by bromodeoxyuridine-flow cytometry technique","volume":"27","author":"JO Fredlund","year":"1994","journal-title":"Cell Prolif"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1432-1033.1997.00232.x","article-title":"Ordered cell cycle phase perturbations in Chinese hamster ovary cells treated with an S-adenosylmethionine decarboxylase inhibitor","volume":"249","author":"JO Fredlund","year":"1997","journal-title":"Eur J Biochem"},{"key":"ref42","first-page":"15","article-title":"Characterization of Pt-, Pd-spermine complexes for their effect on polyamine pathway and cisplatin resistance in A2780 ovarian carcinoma cells","volume":"24","author":"R Tummala","year":"2010","journal-title":"Oncol Rep"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2174\/157018007781788516","article-title":"Effect of the Metal Center on the Antitumor Activity of the Analogous Dinuclear Spermine Chelates (PdCl2)2(Spermine) and (PtCl2)2(Spermine)","volume":"4","author":"AS Soares","year":"2007","journal-title":"Lett Drug Des Discov"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00726-009-0400-2","article-title":"The polyamine transport system as a target for anticancer drug development","volume":"38","author":"AJ Palmer","year":"2010","journal-title":"Amino Acids"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0020-711X(90)90332-W","article-title":"Polyamine transport in mammalian cells","volume":"22","author":"N Seiler","year":"1990","journal-title":"Int J Biochem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/onc.2011.384","article-title":"Molecular mechanisms of cisplatin resistance","volume":"31","author":"L Galluzzi","year":"2012","journal-title":"Oncogene"},{"key":"ref47","first-page":"2769","article-title":"A novel polyamine analog inhibits growth and induces apoptosis in human breast cancer cells","volume":"9","author":"Y Huang","year":"2003","journal-title":"Clin Cancer Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1021\/jm960854n","article-title":"Preparation, characterization, DNA binding, and in vitro cytotoxicity of the enantiomers of the platinum(II) complexes N-methyl-, N-ethyl- and N,N-dimethyl-(R)- and -(S)-3-aminohexahydroazepinedichloroplatinum(II)","volume":"40","author":"EM Rezler","year":"1997","journal-title":"J Med Chem"},{"key":"ref49","first-page":"6075","article-title":"Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10","volume":"50","author":"HD Soule","year":"1990","journal-title":"Cancer Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/gcc.20438","article-title":"High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization","volume":"46","author":"G Jonsson","year":"2007","journal-title":"Genes Chromosomes Cancer"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/01.LAB.0000060030.10652.8C","article-title":"Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier","volume":"83","author":"OT Johannsson","year":"2003","journal-title":"Lab Invest"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/S0021-9258(18)62370-1","article-title":"On the purification of L-ornithine decarboxylase from rat prostate and effects of thiol compounds on the enzyme","volume":"246","author":"J Janne","year":"1971","journal-title":"J Biol Chem"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/cyto.990010309","article-title":"Preparation of tissues for DNA flow cytometric analysis","volume":"1","author":"JT Thornthwaite","year":"1980","journal-title":"Cytometry"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.3168\/jds.2008-1851","article-title":"Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line","volume":"92","author":"C Freiburghaus","year":"2009","journal-title":"J Dairy Sci"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1097\/CAD.0b013e32833f2f77","article-title":"Reduction of the putative CD44+CD24\u2212 breast cancer stem cell population by targeting the polyamine metabolic pathway with PG11047","volume":"21","author":"H Cirenajwis","year":"2010","journal-title":"Anticancer Drugs"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1475-2867-12-20","article-title":"Increased toxicity of a trinuclear Pt-compound in a human squamous carcinoma cell line by polyamine depletion","volume":"12","author":"J Wennerberg","year":"2012","journal-title":"Cancer Cell Int"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/(SICI)1098-2280(1997)30:2<139::AID-EM6>3.0.CO;2-I","article-title":"Comet assay in human biomonitoring studies: reliability, validation, and applications","volume":"30","author":"A Collins","year":"1997","journal-title":"Environ Mol Mutagen"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1089\/dna.2008.0750","article-title":"Polyamine depletion with two different polyamine analogues causes DNA damage in human breast cancer cell lines","volume":"27","author":"VM Johansson","year":"2008","journal-title":"DNA Cell Biol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/(SICI)1097-4644(19991001)75:1<46::AID-JCB5>3.0.CO;2-N","article-title":"Topoisomerase II is nonfunctional in polyamine-depleted cells","volume":"75","author":"K Alm","year":"1999","journal-title":"J Cell Biochem"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0055651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T12:39:18Z","timestamp":1644323958000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0055651"}},"subtitle":[],"editor":[{"given":"Elad","family":"Katz","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,2,13]]},"references-count":59,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,2,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0055651","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718021240.793479004","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,13]]}}}