DNA damage induced by the anthracycline cosmomycin D in DNA repair-deficient cells

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dc.contributor.authorCarvalho, Helotonio [UNIFESP]
dc.contributor.authorGarrido, Leandro M.
dc.contributor.authorFurlan, Renata L. A.
dc.contributor.authorPadilla, Gabriel
dc.contributor.authorAgnoletto, Mateus
dc.contributor.authorGuecheva, Temenouga
dc.contributor.authorHenriques, Joao A. P.
dc.contributor.authorSaffi, Jenifer
dc.contributor.authorMartins Menck, Carlos Frederico
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Rio Grande do Sul
dc.date.accessioned2016-01-24T13:59:30Z
dc.date.available2016-01-24T13:59:30Z
dc.date.issued2010-04-01
dc.description.abstractAnthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side effects related to cardiotoxicity. New anthracyclines have been designed and tested, but the first ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. the anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene.We assessed the induction of apoptosis (Sub-G(1)) by cosmomycin D in nucleotide excision repair-deficient fibroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay).Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with highest apoptosis levels observed 96 h after treatment. the effects of cosmomycin D were equivalent to those obtained with doxorubicin. the broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells, and DNA damage induced by cosmomycin D was confirmed by alkaline comet assay.Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deficient fibroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to differences in structure between cosmomycin D and doxorubicin.en
dc.description.affiliationUniv São Paulo, Dept Microbiol, Inst Biomed Sci, BR-05508900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.description.affiliationUniv Fed Rio Grande do Sul, Dept Biophys, Porto Alegre, RS, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent989-994
dc.identifierhttp://dx.doi.org/10.1007/s00280-010-1244-x
dc.identifier.citationCancer Chemotherapy and Pharmacology. New York: Springer, v. 65, n. 5, p. 989-994, 2010.
dc.identifier.doi10.1007/s00280-010-1244-x
dc.identifier.issn0344-5704
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32404
dc.identifier.wosWOS:000274655500020
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofCancer Chemotherapy and Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectDNA repairen
dc.subjectCosmomycin Den
dc.subjectApoptosisen
dc.subjectAnthracyclinesen
dc.titleDNA damage induced by the anthracycline cosmomycin D in DNA repair-deficient cellsen
dc.typeinfo:eu-repo/semantics/article
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