Curcumin Combined With Turmerones, Essential Oil Components of Turmeric, Abolishes Inflammation-Associated Mouse Colon Carcinogenesis

Biofactors. Mar-Apr 2013;39(2):221-32. doi: 10.1002/biof.1054. Epub 2012 Dec 11.

Abstract

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Cell Line
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / genetics
  • Colitis / metabolism
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control
  • Curcuma
  • Curcumin / therapeutic use*
  • Female
  • Ketones / therapeutic use*
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred ICR
  • Plant Extracts / therapeutic use*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sesquiterpenes / therapeutic use*

Substances

  • Ketones
  • Lipopolysaccharides
  • Plant Extracts
  • Sesquiterpenes
  • ar-turmerone
  • turmeric extract
  • Curcumin