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Role of curcumin and the inhibition of NF-κB in the onset of chemotherapy-induced mucosal barrier injury

Leukemia volume 18, pages 276–284 (2004)Cite this article

Abstract

The inhibition of nuclear factor kappa B (NF-κB) by, for instance, curcumin is becoming an important new approach in combination with chemotherapy or irradiation for the treatment of a variety of cancers including haematological malignancies. A dose-limiting side effect of anticancer therapy in the gastrointestinal tract is mucosal barrier injury. It is hypothesised that mucosal barrier injury is initiated and amplified by proinflammatory-and NF-κB-regulated mediators. Therefore, the effect of NF-κB inhibition was studied in the onset of mucosal barrier injury. In response to cytostatic drug treatment (arabinoside cytosine (Ara-C) and methotrexate (MTX)), NF-κB was activated in intestinal epithelial cells (IEC-6) resulting in an NF-κB-related induction of tumour necrosis factor alpha and monocyte chemoattractant protein-1. NF-κB inhibition increased the susceptibility of IEC-6 cells to Ara-C as well as MTX-induced cell death when obtained by the addition of caffeic acid phenethyl ester (CAPE), but not using curcumin. In an animal model for MTX-induced mucosal barrier injury, the induction of NF-κB-related cytokines and chemokines was detected upon treatment with MTX. Despite increased susceptibility shown in vitro, the inhibition of NF-κB resulted in a partial amelioration of villous atrophy normally seen in the small intestine upon MTX treatment. These results show that the inhibition of NF-κB does not increase intestinal side effects of the anticancer treatment, suggesting a safe use of curcumin and CAPE in combination with anticancer treatment.

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Acknowledgements

We thank all biotechnicians of the small animal facility in Wageningen for housing and assistance with the performance of the animal experiments.

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Authors and Affiliations

  1. Department of Condition and Disease Specific Research, Numico-Research, CA, Wageningen, The Netherlands

    B van't Land, J Marteijn, S Timal & L M'Rabet

  2. Department of Haematology, University Medical Center St Radboud, Nijmegen, The Netherlands

    N M A Blijlevens, J P Donnelly & T J M de Witte

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  1. B van't Land
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Correspondence to L M'Rabet.

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van't Land, B., Blijlevens, N., Marteijn, J. et al. Role of curcumin and the inhibition of NF-κB in the onset of chemotherapy-induced mucosal barrier injury. Leukemia 18, 276–284 (2004). https://doi.org/10.1038/sj.leu.2403233

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