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Apoptosis

Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease

Leukemia volume 17, pages 568–575 (2003)Cite this article

Abstract

Current therapies for Burkitt's lymphoma (BL) utilise combined cytotoxic chemotherapy, but these treatments are not always available in areas where the disease is endemic and are also markedly less successful in AIDS-related BL. Therefore, additional therapies are urgently required. We demonstrate here that combined fibrates and MPA exert powerful, antiproliferative actions against well-characterised Daudi, Raji and L3055 BL cell lines and primary BL cells. Detailed studies in L3055 demonstrated that this activity was mediated by induced apoptosis and confirmed by observations that overexpression of the antiapoptotic genes bcl-2 or bcl-xL conferred significant protection against the drugs. Importantly, since fibrates and MPA are inexpensive and stable with minimal-associated toxicities, we suggest that these drugs should be considered as adjuncts to currently available treatments for BL in endemic and AIDS-related disease.

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Acknowledgements

SLF and QTL contributed equally to this study. This work was funded by grants from the Leukaemia Research Fund (LRF), the Medical Research Council and the West Midlands Health Authority Locally Organized Research Scheme. CMB is the recipient of an LRF Bennett Senior Research Fellowship. JG is a Medical Research Council Professor whose work is supported by an MRC Programme Grant.

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Author notes

  1. K J W Mustard

    Present address: Division of Molecular Physiology, School of Life Sciences, The Wellcome Trust Biocentre, University of Dundee, Dundee, DD1 5EH, UK

  2. J Pound

    Present address: Institute of Cell, Animal and Population Biology, University of Edinburgh Ashworth Laboratories, King's Buildings, Edinburgh, EH9 3JT, UK

Authors and Affiliations

  1. Division of Medical Sciences, University of Birmingham, Birmingham, UK

    S L Fenton & J C Desmond

  2. School of Biosciences, University of Birmingham, Birmingham, UK

    Q T Luong & C M Bunce

  3. School of Biosciences, University of Birmingham, Birmingham, UK

    A Sarafeim, K J W Mustard, J Pound, J Gordon & M T Drayson

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Fenton, S., Luong, Q., Sarafeim, A. et al. Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease. Leukemia 17, 568–575 (2003). https://doi.org/10.1038/sj.leu.2402843

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