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Cancer Prevention Research
Cancer Prevention Research
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Research Article

Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia

Robert E. Carroll, Richard V. Benya, Danielle Kim Turgeon, Shaiju Vareed, Malloree Neuman, Luz Rodriguez, Madhuri Kakarala, Philip M. Carpenter, Christine McLaren, Frank L. Meyskens Jr and Dean E. Brenner
Robert E. Carroll
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Richard V. Benya
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Danielle Kim Turgeon
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Shaiju Vareed
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Malloree Neuman
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Luz Rodriguez
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Madhuri Kakarala
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Philip M. Carpenter
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Christine McLaren
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Frank L. Meyskens Jr
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Dean E. Brenner
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DOI: 10.1158/1940-6207.CAPR-10-0098 Published March 2011
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This article has a correction. Please see:

  • Correction: Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia - December 4, 2012

Abstract

Curcumin is derived from the spice tumeric and has antiinflammatory and antineoplastic effects in vitro and in animal models, including preventing aberrant crypt foci (ACF) and adenomas in murine models of colorectal carcinogenesis. Inhibiting the production of the procarcinogenic eicosanoids prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5-HETE) can suppress carcinogenesis in rodents. Curcumin reduces mucosal concentrations of PGE2 (via inhibition of cyclooxygenases 1 and 2) and 5-HETE (via inhibition of 5-lipoxygenase) in rats. Although preclinical data support curcumin activity in many sites, the poor bioavailability reported for this agent supports its use in the colorectum. We assessed the effects of oral curcumin (2 g or 4 g per day for 30 days) on PGE2 within ACF (primary endpoint), 5-HETE, ACF number, and proliferation in a nonrandomized, open-label clinical trial in 44 eligible smokers with eight or more ACF on screening colonoscopy. We assessed pre- and posttreatment concentrations of PGE2 and 5-HETE by liquid chromatography tandem mass spectroscopy in ACF and normal-tissue biopsies; ACF number via rectal endoscopy; proliferation by Ki-67 immunohistochemistry; and curcumin concentrations by high-performance liquid chromatography in serum and rectal mucosal samples. Forty-one subjects completed the study. Neither dose of curcumin reduced PGE2 or 5-HETE within ACF or normal mucosa or reduced Ki-67 in normal mucosa. A significant 40% reduction in ACF number occurred with the 4-g dose (P < 0.005), whereas ACF were not reduced in the 2-g group. The ACF reduction in the 4-g group was associated with a significant, five-fold increase in posttreatment plasma curcumin/conjugate levels (versus pretreatment; P = 0.009). Curcumin was well tolerated at both 2 g and 4 g. Our data suggest that curcumin can decrease ACF number, and this is potentially mediated by curcumin conjugates delivered systemically. Cancer Prev Res; 4(3); 354–64. ©2011 AACR.

Read the Commentary on this article by Shureiqi et al., p. 296

Footnotes

  • Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).

  • Received June 15, 2010.
  • Revision received November 30, 2010.
  • Accepted January 17, 2011.
  • ©2011 American Association for Cancer Research.
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Cancer Prevention Research: 4 (3)
March 2011
Volume 4, Issue 3
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Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia
Robert E. Carroll, Richard V. Benya, Danielle Kim Turgeon, Shaiju Vareed, Malloree Neuman, Luz Rodriguez, Madhuri Kakarala, Philip M. Carpenter, Christine McLaren, Frank L. Meyskens Jr and Dean E. Brenner
Cancer Prev Res March 1 2011 (4) (3) 354-364; DOI: 10.1158/1940-6207.CAPR-10-0098

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Phase IIa Clinical Trial of Curcumin for the Prevention of Colorectal Neoplasia
Robert E. Carroll, Richard V. Benya, Danielle Kim Turgeon, Shaiju Vareed, Malloree Neuman, Luz Rodriguez, Madhuri Kakarala, Philip M. Carpenter, Christine McLaren, Frank L. Meyskens Jr and Dean E. Brenner
Cancer Prev Res March 1 2011 (4) (3) 354-364; DOI: 10.1158/1940-6207.CAPR-10-0098
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