Review Camptothecin: Current Perspectives

Li, Qingyong; Zu, Yuangang; Shi, Rong-Zhen; Yao, Liping

doi:10.2174/092986706777585004

Cited by 245 publications

(121 citation statements)

References 55 publications

(81 reference statements)

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“…The results of our study confirm the findings of previous studies in mouse bone marrow cells for camptothecin [Backer et al, 1990;Holmström and Winters, 1992], topotecan [Aydemir and Bilaloglu, 2003], and irinotecan [Hardman et al, 2002]. Under the conditions described, topotecan was the most genotoxic compound, followed by camptothecin then irinotecan, probably because substitutions of amino groups for the 9-carbon of the camptothecin A ring lead to compounds with greater in vivo activity [Li et al, 2006]. These replacements greatly increase the antitumor activity of topotecan compared with the camptothecin parent molecule, and could be responsible for its higher genetic toxicity in the somatic mouse bone marrow cells.…”

Section: Resultssupporting

confidence: 90%

“…The antitumor activity of camptothecin is thought to be due to its ability to stabilize the reversible covalent DNAtopoisomerase I complex [Hsiang et al, 1985;Giovanella et al, 1989;Liu et al, 2000;Li et al, 2006;Pommier, 2006;Hartmann and Lipp 2006], preventing the religation step of the breakage/rejoining reaction mediated by the enzyme. The net result is that the drug causes fragmentation of chromosomal DNA, cell death and extensive sister chromatid exchange and chromosomal aberrations [Hsiang et al, 1989;Backer et al, 1990;Holmström and Winters, 1992;Mosesso et al, 2000;Sortibrán et al, 2006;Orta et al, 2008].…”

Section: Introductionmentioning

confidence: 99%

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Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

Attia

Aleisa

Bakheet

et al. 2009

Environ and Mol Mutagen

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We used the conventional bone marrow micronucleus test complemented with the fluorescent in situ hybridization with the minor satellite DNA probe to investigate the mechanisms of induction of micronuclei in mice treated with camptothecin and its clinical antineoplastic analogues topotecan and irinotecan. All experiments were performed with male Swiss albino mice. Single doses of 1 mg/kg camptothecin or 0.6 mg/kg topotecan were injected intraperitoneally and bone marrow was sampled at 30 hr (camptothecin) or 24 hr (topotecan) after treatment. A dose of 60 mg/kg irinotecan was injected intravenously, once every fourth day for 13 days and bone marrow was sampled 24 hr after the last treatment. In animals treated with camptothecin, a total of 1.07% micronuclei were found and 70% of them were centromere-negative, indicating their formation by DNA strand breaks and reflecting the predominant clastogenic activity of camptothecin. Exposure to topotecan and irinotecan yielded 1.71 and 0.83% micronuclei, respectively. About 52.7 and 48.8% of the induced micronuclei, respectively, were centromere-positive, indicating their formation by whole chromosomes and reflecting the aneugenic activity of both compounds. Correspondingly, about 47.3 and 51.2% of the induced micronuclei, respectively were centromere-negative, demonstrating that topotecan and irinotecan not only induce chromosome loss but also DNA strand breaks. Both the clastogenic and aneugenic potential of these drugs can lead to the development of secondary tumors and abnormal reproductive outcomes. Therefore, the clinical use of these agents must be weighed against the risks of secondary malignancies in cured patients and persistent genetic damage of their potential offspring.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

Attia

Aleisa

Bakheet

et al. 2009

Environ and Mol Mutagen

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“…An example can be found in camptothecin which is a renowned anti-cancer compound that can be extracted from Nyssaceae arbo (Wen et al, 2005). It is worth mentioning that camptothecin is not a perfect and inexhaustible compound in cancer treatment because of the side-effect on gastrointestinal system and bone marrow, and moderate solubility in aqueous media (Zhu et al, 1978;Kehrer et al, 2001;Li et al, 2006). However, 10-hydroxycamptothecin, which can also be extracted from Nyssaceae arbo exists at a low content of 0.001% but shows higher anti-cancer activity and lower side-effect compared to camptothecin.…”

Section: To Improve Existing Anti-cancer Drugsmentioning

confidence: 99%

Biotransformation, a Promising Technology for Anti-cancer Drug Development

Gao

Zhang²,

Wang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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With the high morbidity and mortality caused by cancer, finding new and more effective anti-cancer drugs is very urgent. In current research, biotransformation plays a vital role in the research and development of cancer drugs and has obtained some achievements. In this review, we have summarized four applications as follows: to exploit novel anti-cancer drugs, to improve existing anti-cancer drugs, to broaden limited anti-cancer drug resources and to investigate correlative mechanisms. Three different groups of important anti-cancer compounds were assessed to clarify the current practical applications of biotransformation in the development of anti-cancer drugs.

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“…Interest in camptothecin increased in the 1980s and 90s, after the discovery of its mechanism of action based on inhibition of nuclear enzyme topoisomerase I which is involved in DNA replication [3]. This interest resulted in the synthesis of many analogues, two of which were introduced as a medicine in anticancer therapy (topotecan, irinotecan), while some other are at the stage of clinical trials [4]. Camptothecins exist in two forms: lactone, stable at pH<5.…”

Section: Introductionmentioning

confidence: 99%

Determination of the Protein-Binding Properties of Camptothecins by Means of Optical Spectroscopy Methods

et al. 2014

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Optical spectroscopy methods are widely used in studies of drugs. The a nity of camptothecins anticancer agents to human serum albumin (HSA) was determined in this work. Camptothecins (CPTs) exist in two forms: active lactone and open ring inactive carboxylate. In blood, the hydrolysis process of lactone form occurs which leads to deactivation of CPTs. Research is being done on biophysical properties of synthesized CPT compounds, in particular on binding to albumin. The a nity to plasma proteins is an important determinant of stability of CPTs in blood. The following analogues of CPT were tested in this paper: irinotecan, SN-38, topotecan, and 9-amino camptothecin. Using the method of uorescence anisotropy measurement, the association constants of the studied compounds to HSA were determined. The authors attempted to determine the deactivation rate of topotecan in HSA solution using Principal Component Analysis and Factor Analysis of absorption spectra recorded during hydrolysis process of lactone form.

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Review Camptothecin: Current Perspectives

Cited by 245 publications

References 55 publications

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

Biotransformation, a Promising Technology for Anti-cancer Drug Development

Determination of the Protein-Binding Properties of Camptothecins by Means of Optical Spectroscopy Methods

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