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

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

Author Carvalho, Helotonio Autor UNIFESP Google Scholar
Garrido, Leandro M. Google Scholar
Furlan, Renata L. A. Google Scholar
Padilla, Gabriel Google Scholar
Agnoletto, Mateus Google Scholar
Guecheva, Temenouga Google Scholar
Henriques, Joao A. P. Google Scholar
Saffi, Jenifer Google Scholar
Martins Menck, Carlos Frederico Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Sul
Abstract Anthracyclines 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.
Keywords DNA repair
Cosmomycin D
Apoptosis
Anthracyclines
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2010-04-01
Published in Cancer Chemotherapy and Pharmacology. New York: Springer, v. 65, n. 5, p. 989-994, 2010.
ISSN 0344-5704 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 989-994
Origin http://dx.doi.org/10.1007/s00280-010-1244-x
Access rights Closed access
Type Article
Web of Science ID WOS:000274655500020
URI http://repositorio.unifesp.br/handle/11600/32404

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