PMID- 10557090
OWN - NLM
STAT- MEDLINE
DCOM- 19991203
LR  - 20231213
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 44
DP  - 1999 Oct 28
TI  - Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive 
      agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK 
      signalling complex.
PG  - 6013-20
AB  - Colorectal cancer is a major cause of cancer deaths in Western countries, but 
      epidemiological data suggest that dietary modification might reduce these by as 
      much as 90%. Cyclo-oxygenase 2 (COX2), an inducible isoform of prostaglandin H 
      synthase, which mediates prostaglandin synthesis during inflammation, and which 
      is selectively overexpressed in colon tumours, is thought to play an important 
      role in colon carcinogenesis. Curcumin, a constituent of turmeric, possesses 
      potent anti-inflammatory activity and prevents colon cancer in animal models. 
      However, its mechanism of action is not fully understood. We found that in human 
      colon epithelial cells, curcumin inhibits COX2 induction by the colon tumour 
      promoters, tumour necrosis factor alpha or fecapentaene-12. Induction of COX2 by 
      inflammatory cytokines or hypoxia-induced oxidative stress can be mediated by 
      nuclear factor kappa B (NF-kappaB). Since curcumin inhibits NF-kappaB activation, 
      we examined whether its chemopreventive activity is related to modulation of the 
      signalling pathway which regulates the stability of the NF-kappaB-sequestering 
      protein, IkappaB. Recently components of this pathway, NF-kappaB-inducing kinase 
      and IkappaB kinases, IKKalpha and beta, which phosphorylate IkappaB to release 
      NF-kappaB, have been characterised. Curcumin prevents phosphorylation of IkappaB 
      by inhibiting the activity of the IKKs. This property, together with a long 
      history of consumption without adverse health effects, makes curcumin an 
      important candidate for consideration in colon cancer prevention.
FAU - Plummer, S M
AU  - Plummer SM
AD  - MRC Toxicology Unit, University of Leicester, Leicester, LE1 9HN, UK.
FAU - Holloway, K A
AU  - Holloway KA
FAU - Manson, M M
AU  - Manson MM
FAU - Munks, R J
AU  - Munks RJ
FAU - Kaptein, A
AU  - Kaptein A
FAU - Farrow, S
AU  - Farrow S
FAU - Howells, L
AU  - Howells L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Caffeic Acids)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Polyenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 84000-59-9 (1-(1-glycero)dodeca-1,3,5,7,9-pentaene)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - G960R9S5SK (caffeic acid phenethyl ester)
RN  - IT942ZTH98 (Curcumin)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Caffeic Acids/pharmacology
MH  - Colonic Neoplasms/*drug therapy/*metabolism
MH  - Curcumin/*pharmacology
MH  - Cyclooxygenase 2
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/*pharmacology
MH  - Humans
MH  - I-kappa B Kinase
MH  - I-kappa B Proteins/drug effects/metabolism
MH  - Isoenzymes/drug effects/*metabolism
MH  - Membrane Proteins
MH  - NF-kappa B/*drug effects/genetics/metabolism
MH  - Phenylethyl Alcohol/analogs & derivatives/pharmacology
MH  - Polyenes/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/drug effects/*metabolism
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism
MH  - Signal Transduction
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - NF-kappaB-Inducing Kinase
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - 10.1038/sj.onc.1202980 [doi]
PST - ppublish
SO  - Oncogene. 1999 Oct 28;18(44):6013-20. doi: 10.1038/sj.onc.1202980.