The DOI matches its Crossref record.
Mechanism of Action of Camptothecin
Abstract
A bstract: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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Dolma, S., Lessnick, S. L., Hahn, W. C., & Stockwell, B. R. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00050-3 · Cited by 1,446
In vivo dynamics of RNA polymerase II transcription
Darzacq, X., Shav-Tal, Y., de Turris, V., Brody, Y., Shenoy, S. M., Phair, R. D., & Singer, R. H. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1280 · Cited by 665
Furuta, T., Takemura, H., Liao, Z.-Y., Aune, G. J., Redon, C., Sedelnikova, O. A., Pilch, D. R., Rogakou, E. P., Celeste, A., Chen, H. T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300198200 · Cited by 449
Almeida, K. H., & Sobol, R. W. (2007) · DNA Repair · doi:10.1016/j.dnarep.2007.01.009 · Cited by 437
Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity.
Xu, Y., & Villalona-Calero, M. A. (2002) · Annals of Oncology · doi:10.1093/annonc/mdf337 · Cited by 413
Dixon, S. J. (2017) · Immunological Reviews · doi:10.1111/imr.12533 · Cited by 314
Topoisomerase I-Mediated Inhibition of Hypoxia-Inducible Factor 1
Rapisarda, A., Uranchimeg, B., Sordet, O., Pommier, Y., Shoemaker, R. H., & Melillo, G. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3139 · Cited by 301
Wan, S., Pestka, S., Jubin, R. G., Lyu, Y. L., Tsai, Y.-C., & Liu, L. F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032542 · Cited by 295
Self-citationRole of p21 in Apoptosis and Senescence of Human Colon Cancer Cells Treated with Camptothecin
Han, Z., Wei, W., Dunaway, S., Darnowski, J. W., Calabresi, P., Sedivy, J., Hendrickson, E. A., Balan, K. V., Pantazis, P., & Wyche, J. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112401200 · Cited by 262
Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA‐PK
Das, B. B., Antony, S., Gupta, S., Dexheimer, T. S., Redon, C. E., Garfield, S., Shiloh, Y., & Pommier, Y. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.302 · Cited by 151
Biological mechanism profiling using an annotated compound library
Root, D. E., Flaherty, S. P., Kelley, B. P., & Stockwell, B. R. (2003) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.08.009 · Cited by 95
Transient ATM Kinase Inhibition Disrupts DNA Damage–Induced Sister Chromatid Exchange
White, J. S., Choi, S., & Bakkenist, C. J. (2010) · Science Signaling · doi:10.1126/scisignal.2000758 · Cited by 66
Andreopoulou, E., & Sparano, J. A. (2013) · Current Breast Cancer Reports · doi:10.1007/s12609-012-0097-1 · Cited by 65
Guérin, E., Raffelsberger, W., Pencreach, E., Maier, A., Neuville, A., Schneider, A., Bachellier, P., Rohr, S., Petitprez, A., Poch, O., et al. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00120 · Cited by 44
Metadata
- Authors
- LIU, L. F., DESAI, S. D., LI, T., MAO, Y., SUN, M., & SIM, S.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 922
- Issue
- 1
- Pages
- 1-10
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W4297069849
- Cited by
- 476
- References
- 0
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
