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

Abstract

The inhibition of nuclear factor kappa B (NF-kappaB) 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-kappaB-regulated mediators. Therefore, the effect of NF-kappaB inhibition was studied in the onset of mucosal barrier injury. In response to cytostatic drug treatment (arabinoside cytosine (Ara-C) and methotrexate (MTX)), NF-kappaB was activated in intestinal epithelial cells (IEC-6) resulting in an NF-kappaB-related induction of tumour necrosis factor alpha and monocyte chemoattractant protein-1. NF-kappaB 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-kappaB-related cytokines and chemokines was detected upon treatment with MTX. Despite increased susceptibility shown in vitro, the inhibition of NF-kappaB 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-kappaB does not increase intestinal side effects of the anticancer treatment, suggesting a safe use of curcumin and CAPE in combination with anticancer treatment.

• Authors: B van't Land, N M A Blijlevens, J Marteijn, S Timal, J P Donnelly, T J M de Witte, L M'Rabet
• Journal: Leukemia (Leukemia) Vol. 18 Issue 2 Pg. 276-84 (Feb 2004) ISSN: 0887-6924 [Print] England
• PMID: 14671640 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Caffeic Acids
• NF-kappa B
• Cytarabine
• caffeic acid phenethyl ester
• Curcumin
• Phenylethyl Alcohol
• Methotrexate

Topics

• Animals
• Antineoplastic Agents (adverse effects)
• Caffeic Acids (pharmacology)
• Cell Line
• Curcumin (pharmacology)
• Cytarabine (pharmacology)
• Drug Interactions
• Female
• Intestinal Mucosa (cytology, drug effects, pathology)
• Methotrexate (pharmacology)
• NF-kappa B (agonists, antagonists & inhibitors)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Rats
• Rats, Inbred Strains