Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair
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- 1 August 2001
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 7 (8) , 961-966
- https://doi.org/10.1038/91008
Abstract
While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wild-type genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSB) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks.Keywords
This publication has 33 references indexed in Scilit:
- Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathwaysInternational Journal of Cancer, 2001
- Ecteinascidin-743: A Marine-Derived Compound in Advanced, Pretreated Sarcoma Patients—Preliminary Evidence of ActivityJournal of Clinical Oncology, 2001
- Phase I and Pharmacokinetic Study of Ecteinascidin-743, a New Marine Compound, Administered as a 24-hour Continuous Infusion in Patients With Solid TumorsJournal of Clinical Oncology, 2001
- Antitumor compounds from tunicatesMedicinal Research Reviews, 2000
- Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor grooveProceedings of the National Academy of Sciences, 1999
- Phthalascidin, a synthetic antitumor agent with potency and mode of action comparable to ecteinascidin 743Proceedings of the National Academy of Sciences, 1999
- Molecular Basis for the DNA Sequence Selectivity of Ecteinascidin 736 and 743: Evidence for the Dominant Role of Direct Readout via Hydrogen BondingJournal of the American Chemical Society, 1998
- DNA Sequence- and Structure-Selective Alkylation of Guanine N2 in the DNA Minor Groove by Ecteinascidin 743, a Potent Antitumor Compound from the Caribbean Tunicate Ecteinascidia turbinataBiochemistry, 1996
- Additional antitumor ecteinascidins from a Caribbean tunicate: crystal structures and activities in vivo.Proceedings of the National Academy of Sciences, 1992
- Bioactive Compounds from Aquatic and Terrestrial SourcesJournal of Natural Products, 1990