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RNA synthesis block by 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells

Oncogene volume 18, pages 5765–5772 (1999)Cite this article

Abstract

Most modern chemo- and radiotherapy treatments of human cancers use the DNA damage pathway, which induces a p53 response leading to either G1 arrest or apoptosis. However, such treatments can induce mutations and translocations leading to secondary malignancies or recurrent disease, which often have a poor prognosis because of resistance to therapy. Here we report that 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB), an inhibitor of CDK7 TFIIH-associated kinase, CKI and CKII kinases, blocking RNA polymerase II in the early elongation stage, triggers p53-dependent apoptosis in human colon adenocarcinoma cells in a transcription independent manner. The fact that DRB kills tumour-derived cells without employment of DNA damage gives rise to the possibility of the development of a new alternative chemotherapeutic treatment of tumours expressing wild type p53, with a decreased risk of therapy-related, secondary malignancies.

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Acknowledgements

We would like to thank Jo Milner and Carlos Rubbi for the critical reading of the manuscript and helpful discussions. This work was supported by the Joint Research Board of St Bartholomew's Hospital and the ICRF to Robert H te Poele and Simon P Joel and by the YCR to Andrei L Okorokov.

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  1. Robert H te Poele

    Present address: CRC Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey, SM2 4NG, UK

Authors and Affiliations

  1. ICRF Department of Medical Oncology, Barry Reed Oncology Laboratory, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK

    Robert H te Poele & Simon P Joel

  2. Department of Biology, Yorkshire Cancer Research P53 Research Group, University of York, Heslington, York, YO10 5DD, UK

    Andrei L Okorokov

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te Poele, R., Okorokov, A. & Joel, S. RNA synthesis block by 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) triggers p53-dependent apoptosis in human colon carcinoma cells. Oncogene 18, 5765–5772 (1999). https://doi.org/10.1038/sj.onc.1202961

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