Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line

Abal, Miguel; Bras-Gonçalves, Rui; Judde, Jean-Gabriel; Fsihi, Hafida; Crémoux, Patricia de; Louvard, Daniel; Magdelénat, H.; Robine, Sylvie; Poupon, Marie‐France

doi:10.1038/sj.onc.1207299

Cited by 43 publications

(33 citation statements)

References 26 publications

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“…A reduction in cyclin B1 protein levels after roscovitine and CPT treatment had been previously reported for synchronised HT29 cells (Abal et al, 2004). The reduction is likely indirectly due to inhibition of CDK7/CDK9 complexes, whose activities are required for transcription of a variety of mRNAs including cyclin B1 and anti-apoptotic genes (MacCallum et al, 2005).…”

Section: Discussionmentioning

confidence: 62%

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Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

et al. 2006

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We have studied the role of cyclins and cyclin-dependent kinase (CDK) activity in apoptosis induced by camptothecin (CPT). In this model, 22% of the cells stain for annexin-V at 24 h and then proceed to be 93% positive by 72 h. This time window permits the analysis of cyclins in cells that are committed to apoptosis but not yet dead. We provide evidence that cyclin protein levels and then associated kinase levels increase after CPT treatment. Strikingly, cyclin B1 and cyclin E1 proteins are present at the same time in CPT treated HT29 cells. Although cyclin B1 and E1 CDK complexes are activated in CPT treated cells, only the cyclin B1 complex is required for apoptosis since reduction of cyclin B1 by RNAi or roscovitine treatment reduces the number of annexin-V-stained cells. We have detected poorly organized chromosomes and phosphorylated histone H3 epitopes at the time of maximum cyclin B1/CDK kinase activity in CPT-treated cells, which suggests that these cells enter a mitotic catastrophe. Understanding which CDKs are required for apoptosis may allow us to better adapt CDK inhibitors for use as anti-cancer compounds.

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Section: Discussionmentioning

confidence: 62%

“…For example, roscovitine may enhance the activity of CPT derivatives in vivo (Abal et al, 2004), via its effects on transcription in addition to its effects upon CDK1 and CDK2 (MacCallum et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

et al. 2006

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“…In fact, certain epithelial cell lines do not follow the p53-dependent dichotomous reaction to DNA damage described in the present work and by other authors in colon carcinomas (Bunz et al, 1998;te Poele and Joel, 1999;Andreassen et al, 2001a;Magrini et al, 2002) and glioblastomas (Wang et al, 2004). For example, an HT-29A4 clone with a dominantly expressed p53 wt described by Abal et al (2004) shows a sustained cell cycle arrest and apoptosis after CPT-11 treatment, and the colon carcinoma cell line KM12 (p53 mut ) arrests transiently in the G2 phase and then proliferates normally (Goldwasser et al, 1996), while irradiated HeLa cells (p53-deficient) perform a lasting G2/M phase arrest, not apoptosis (Crawford and Piwnica-Worms, 2001). The observed dichotomy is not observed in the case of other therapeutics: for example, oxaliplatin induces apoptosis in HCT116 while HCT116p53 À/À cells are resistant (Boyer et al, 2004).…”

Section: Discussionmentioning

confidence: 72%

“…Both, the DNA damage-induced cell cycle arrest as well as apoptosis are related to the p53 mutation status (Bunz et al, 1998;Magrini et al, 2002;Abal et al, 2004). Following DNA damage, the p53 wild-type (p53 wt ) cells have been shown to preferentially undergo a long-term cell cycle arrest, while the p53-mutated (p53 mut ) cells perform apoptosis (Bunz et al, 1998;te Poele and Joel, 1999;Magrini et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth

Notter

et al. 2005

Oncogene

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“…Roscovitine showed synergistic effects in combination with other chemotherapeutic agents in vitro, e.g. camptothecin in MCF-7 breast tumor [121], histone deacetylase (LAQ824) in HL60 and Jurkat leukemic cells, doxorubicin in sarcoma cell lines [122] and irinotecan in p53-mutated colon cancer [123].…”

Section: Meijer Et Al (1997)mentioning

confidence: 99%

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

Zhelev

Trifonov²,

Wang³

et al. 2013

Biodiscovery

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This monograph reviews the discovery and development of the cyclindependent kinase inhibitor roscovitine (R-roscovitine, CYC202, Seliciclib). The authors summarise the in vitro and in vivo data that have formed the basis for clinical investigation of Seliciclib as an anti-cancer drug. Kinase selectivity, cellular effects and the pharmacological properties of the drug are discussed in addition to the clinical results of Seliciclib being reviewed. Novel results on the effect of the drug in cardiac hypertrophy are summarized and potential applications of Seliciclib in other therapeutic areas, including, inflammation, virology, glomerulonephritis and polycystic kidney disease, are discussed. Finally the authors argue that optimisation of the therapeutic effect of kinase inhibitors such as Seliciclib can be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. Seliciclib -discovery and developmentBioDiscovery 2 December 2013 | Issue 10 | 1

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Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line

Cited by 43 publications

References 26 publications

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

Equivalent effect of DNA damage-induced apoptotic cell death or long-term cell cycle arrest on colon carcinoma cell proliferation and tumour growth

From Roscovitine to CYC202 to Seliciclib – from bench to bedside: discovery and development

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