Camptothecin effects on DNA synthesis in murine leukemia cells

Kessel, David; Bosmann, H.Bruce; Löhr, Kristina

doi:10.1016/0005-2787(72)90429-7

Cited by 74 publications

(19 citation statements)

References 10 publications

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“…CPT-11 and TPT) have been introduced into the clinic (4,5). CPT is a TOPO1-targeting anticancer drug which shows high S phase-specific cytotoxicity and induces G2-M cell cycle arrest (6)(7)(8)(9). Previous studies showed that a replication fork collision model has been proposed to explain the S phase cytotoxicity and it is presumably important for the antitumor activity of CPT.…”

Section: Introductionmentioning

confidence: 99%

Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer

Ping¹,

Lee²,

Wu³

et al. 2006

Oncol Rep

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Abstract. 10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. However, its use has been limited due to its water-insolubility and toxicity with i.v. administration. The purpose of this study was to investigate the efficacy, toxicity and proper dosage of 10-HCPT as a single agent by oral administration in the treatment of human colon cancer. 10-HCPT significantly repressed the proliferation of Colo 205 cells at a relatively low concentration (5-20 nM). Flow cytometry analysis and Western blot and apoptosis assays demonstrated that low-dose 10-HCPT arrested Colo 205 cells in the G2 phase of the cell cycle and triggered apoptosis through a caspase-3-dependent pathway. Moreover, following oral administration at doses of 2.5-7.5 mg/kg/2 days, significant suppression of tumor growth by 10-HCPT was observed in mouse xenografts. No acute toxicity was observed after an oral challenge of 10-HCPT in BALB/c-nude mice every 2 days. The results of this study suggest that a relatively low dose of 10-HCPT (p.o.) is able to inhibit the growth of colon cancer, facilitating the development of a new protocol of human trials with this anticancer drug.

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Section: Introductionmentioning

confidence: 99%

Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer

Ping¹,

Lee²,

Wu³

et al. 2006

Oncol Rep

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“…Topoisomerase I inhibitors are S-phase-specific drugs that result in inhibition of RNA synthesis. This effect is rapidly reversible following drug removal, suggesting that prolonged exposure is important for efficacy (17)(18)(19)(20)(21). 9-AC has been shown to be more potent that the mother compound 20-S-Camptothecin and superior to 5-FU for treatment of liver metastases in murine animal models, with significant prolongation of survival (3,(22)(23)(24).…”

Section: Discussionmentioning

confidence: 98%

A comparison of locoregional depot and systemic preparations of 9-aminocamptothecin for treatment of liver metastases in a rat tumor model: Superior antitumor activity of sustained-release preparation

Dookeran

Brumfield

Rubin

1997

Annals of Surgical Oncology

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“…[69][70][71] The drug target of camptothecin is DNA topoisomerase I (topo I), which gets trapped in a complex covalently bound to nicked DNA. 72,73 The major role of DNA topoisomerase I is to relax unconstrained positive and negative superhelicity generated during transcription elongation.…”

Section: Camptothecinmentioning

confidence: 99%

Transcriptional Inhibition by DNA Damage as a Trigger for Cell Death

Ljungman¹

2012

The Cellular Response to the Genotoxic Insult

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Camptothecin effects on DNA synthesis in murine leukemia cells

Cited by 74 publications

References 10 publications

Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer

Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer

A comparison of locoregional depot and systemic preparations of 9-aminocamptothecin for treatment of liver metastases in a rat tumor model: Superior antitumor activity of sustained-release preparation

Transcriptional Inhibition by DNA Damage as a Trigger for Cell Death

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