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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences

Giuseppe Garcea, David P. Berry, Donald J.L. Jones, Raj Singh, Ashley R. Dennison, Peter B. Farmer, Ricky A. Sharma, William P. Steward and Andreas J. Gescher
Giuseppe Garcea
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David P. Berry
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Donald J.L. Jones
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Raj Singh
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Ashley R. Dennison
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Peter B. Farmer
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Ricky A. Sharma
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William P. Steward
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Andreas J. Gescher
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DOI:  Published January 2005
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Abstract

Curcumin, a constituent of the spice turmeric, has been shown to reduce the adenoma burden in rodent models of colorectal cancer accompanied by a reduction of levels of the oxidative DNA adduct 3-(2-deoxy-β-di-erythro-pentafuranosyl)-pyr[1,2-α]-purin-10(3H)one (M1G) and of expression of the enzyme cyclooxygenase-2 (COX-2). We tested the hypothesis that pharmacologically active levels of curcumin can be achieved in the colorectum of humans as measured by effects on levels of M1G and COX-2 protein. Patients with colorectal cancer ingested curcumin capsules (3,600, 1,800, or 450 mg daily) for 7 days. Biopsy samples of normal and malignant colorectal tissue, respectively, were obtained at diagnosis and at 6 to 7 hours after the last dose of curcumin. Blood was taken 1 hour after the last dose of curcumin. Curcumin and its metabolites were detected and quantitated by high-performance liquid chromatography with detection by UV spectrophotometry or mass spectrometry. M1G levels and COX-2 protein expression were measured by immunoslot blot and Western blotting, respectively. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 ± 5.7 and 7.7 ± 1.8 nmol/g, respectively. Curcumin sulfate and curcumin glucuronide were identified in the tissue of these patients. Trace levels of curcumin were found in the peripheral circulation. M1G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). Administration of curcumin (3,600 mg) decreased M1G levels from 4.8 ± 2.9 adducts per 107 nucleotides in malignant colorectal tissue to 2.0 ± 1.8 adducts per 107 nucleotides (P < 0.05 by ANOVA). COX-2 protein levels in malignant colorectal tissue were not affected by curcumin. The results suggest that a daily dose of 3.6 g curcumin achieves pharmacologically efficacious levels in the colorectum with negligible distribution of curcumin outside the gut.

  • Chemoprevention
  • curcumin
  • pharmacodynamics

Footnotes

  • ↵3 Perkins et al., unpublished data.

  • Grant support: UK Medical Research Council programme grant 1995, Association of International Cancer Research project grant 1998, and University Hospitals of Leicester Trust 2000.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Cancer Epidemiology Biomarkers & Prevention: 14 (1)
January 2005
Volume 14, Issue 1
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Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences
Giuseppe Garcea, David P. Berry, Donald J.L. Jones, Raj Singh, Ashley R. Dennison, Peter B. Farmer, Ricky A. Sharma, William P. Steward and Andreas J. Gescher
Cancer Epidemiol Biomarkers Prev January 1 2005 (14) (1) 120-125;

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Consumption of the Putative Chemopreventive Agent Curcumin by Cancer Patients: Assessment of Curcumin Levels in the Colorectum and their Pharmacodynamic Consequences
Giuseppe Garcea, David P. Berry, Donald J.L. Jones, Raj Singh, Ashley R. Dennison, Peter B. Farmer, Ricky A. Sharma, William P. Steward and Andreas J. Gescher
Cancer Epidemiol Biomarkers Prev January 1 2005 (14) (1) 120-125;
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