PMID- 9674701
OWN - NLM
STAT- MEDLINE
DCOM- 19980806
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 17
IP  - 2
DP  - 1998 Jul 16
TI  - Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin.
PG  - 173-8
AB  - Curcumin, a dietary pigment in curry, suppresses tumor initiation and tumor 
      promotion. Curcumin is also a potent inhibitor for AP-1 and NF-kappaB activation. 
      In this report, we show that curcumin inhibits JNK activation by various agonists 
      including PMA plus ionomycin, anisomycin, UV-C, gamma radiation, TNF-alpha, and 
      sodium orthovanadate. Although both JNK and ERK activation by phorbol 
      12-myristate 13-acetate (PMA) plus ionomycin were suppressed by curcumin, the JNK 
      pathway was more sensitive. The IC50 (50% inhibition concentration) of curcumin 
      was between 5-10 microM for JNK activation and was 20 microM for ERK activation. 
      In transfection assays, curcumin moderately suppressed MEKK1-induced JNK 
      activation; however, it effectively blocked JNK activation caused by 
      co-transfection of TAK1, GCK, or HPK1. Curcumin did not directly inhibit JNK, 
      SEK1, MEKK1 or HPK1 activity. Although curcumin suppressed TAK1 and GCK 
      activities at high concentrations, this inhibition cannot fully account for the 
      JNK inhibition by curcumin in vivo. Our data suggest that curcumin may affect the 
      JNK pathway by interfering with the signaling molecule(s) at the same level or 
      proximally upstream of the MAPKKK level. Taken together, the inhibition of the 
      MEKK1-JNK pathway reveals a possible mechanism of suppression of AP-1 and 
      NF-kappaB signaling by curcumin, and may explain the potent anti-inflammatory and 
      anti-carcinogenic effects of this chemical.
FAU - Chen, Y R
AU  - Chen YR
AD  - The Department of Microbiology and Immunology, Baylor College of Medicine, 
      Houston, Texas 77030, USA.
FAU - Tan, T H
AU  - Tan TH
LA  - eng
GR  - R01-AI38649/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Curcumin/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Jurkat Cells
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Signal Transduction/drug effects/radiation effects
MH  - T-Lymphocytes/drug effects
EDAT- 1998/07/23 00:00
MHDA- 1998/07/23 00:01
CRDT- 1998/07/23 00:00
PHST- 1998/07/23 00:00 [pubmed]
PHST- 1998/07/23 00:01 [medline]
PHST- 1998/07/23 00:00 [entrez]
AID - 10.1038/sj.onc.1201941 [doi]
PST - ppublish
SO  - Oncogene. 1998 Jul 16;17(2):173-8. doi: 10.1038/sj.onc.1201941.