Mechanism of Action of Camptothecin
Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-...
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Annals of the New York Academy of Sciences
2006
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| Online Access: | http://ir.unimas.my/id/eprint/8233/ |
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| author | Liu, L.F. Shyamal D., Desai Li, Tsai-Kun Mao, Yong Mei, Sun Sim, S.P |
| author_facet | Liu, L.F. Shyamal D., Desai Li, Tsai-Kun Mao, Yong Mei, Sun Sim, S.P |
| author_sort | Liu, L.F. |
| building | UNIMAS Institutional Repository |
| collection | Online Access |
| description | Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I-mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potential roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed. |
| first_indexed | 2025-11-15T06:22:04Z |
| format | Article |
| id | unimas-8233 |
| institution | Universiti Malaysia Sarawak |
| institution_category | Local University |
| last_indexed | 2025-11-15T06:22:04Z |
| publishDate | 2006 |
| publisher | Annals of the New York Academy of Sciences |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | unimas-82332015-07-03T02:52:04Z http://ir.unimas.my/id/eprint/8233/ Mechanism of Action of Camptothecin Liu, L.F. Shyamal D., Desai Li, Tsai-Kun Mao, Yong Mei, Sun Sim, S.P R Medicine (General) Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I-mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potential roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed. Annals of the New York Academy of Sciences 2006 Article PeerReviewed Liu, L.F. and Shyamal D., Desai and Li, Tsai-Kun and Mao, Yong and Mei, Sun and Sim, S.P (2006) Mechanism of Action of Camptothecin. Annals of New York Academy of Science, 922. ISSN 1749-6632 http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2000.tb07020.x/abstract;jsessionid=8077573930C275ADC499C4011810F5D6.f02t03?userIsAuthenticated=false&deniedAccessCustomisedMessage= 10.1111/j.1749-6632.2000.tb07020.x |
| spellingShingle | R Medicine (General) Liu, L.F. Shyamal D., Desai Li, Tsai-Kun Mao, Yong Mei, Sun Sim, S.P Mechanism of Action of Camptothecin |
| title | Mechanism of Action of Camptothecin |
| title_full | Mechanism of Action of Camptothecin |
| title_fullStr | Mechanism of Action of Camptothecin |
| title_full_unstemmed | Mechanism of Action of Camptothecin |
| title_short | Mechanism of Action of Camptothecin |
| title_sort | mechanism of action of camptothecin |
| topic | R Medicine (General) |
| url | http://ir.unimas.my/id/eprint/8233/ http://ir.unimas.my/id/eprint/8233/ http://ir.unimas.my/id/eprint/8233/ |