Abstract | PURPOSE: METHODS: We assessed the induction of apoptosis (Sub-G1) 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). RESULTS: 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. CONCLUSIONS:
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.
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Authors | Helotonio Carvalho, Leandro M Garrido, Renata L A Furlan, Gabriel Padilla, Mateus Agnoletto, Temenouga Guecheva, João A P Henriques, Jenifer Saffi, Carlos Frederico Martins Menck |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 65
Issue 5
Pg. 989-94
(Apr 2010)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 20107801
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthracyclines
- Antineoplastic Agents
- cosmomycin D
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Topics |
- Anthracyclines
(chemistry, toxicity)
- Antineoplastic Agents
(chemistry, toxicity)
- Apoptosis
(drug effects)
- Cell Line
- Comet Assay
- DNA Damage
- DNA Repair
- Fibroblasts
(drug effects)
- Humans
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