RGD Reference Report - Curcumin induced human gastric cancer BGC-823 cells apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway. - Rat Genome Database

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Curcumin induced human gastric cancer BGC-823 cells apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway.

Authors: Liang, Tao  Zhang, Xiaojian  Xue, Wenhua  Zhao, Songfeng  Zhang, Xiang  Pei, Jianying 
Citation: Liang T, etal., Int J Mol Sci. 2014 Sep 5;15(9):15754-65. doi: 10.3390/ijms150915754.
RGD ID: 150429751
Pubmed: PMID:25198898   (View Abstract at PubMed)
PMCID: PMC4200840   (View Article at PubMed Central)
DOI: DOI:10.3390/ijms150915754   (Journal Full-text)

The signaling mediated by stress-activated MAP kinases (MAPK), c-Jun N-terminal kinase (JNK) has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS) production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion) significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
curcumin increases phosphorylationEXP 150429751Curcumin increases phosphorylation of MAP2K4 protein in uterine cervixRGD 
curcumin increases phosphorylationEXP 150429751Curcumin increases phosphorylation of MAP3K5 protein in uterine cervixRGD 
curcumin increases phosphorylationEXP 150429751Curcumin increases phosphorylation of MAPK8 protein in uterine cervixRGD 
curcumin increases phosphorylationISOMAP2K4 (Homo sapiens)150429751; 150429751Curcumin increases phosphorylation of MAP2K4 protein in uterine cervixRGD 
curcumin increases phosphorylationISOMAP3K5 (Homo sapiens)150429751; 150429751Curcumin increases phosphorylation of MAP3K5 protein in uterine cervixRGD 
curcumin increases phosphorylationISOMAPK8 (Homo sapiens)150429751; 150429751Curcumin increases phosphorylation of MAPK8 protein in uterine cervixRGD 
N-acetyl-L-cysteine multiple interactionsEXP 150429751N-acetyl-L-cysteine inhibits the reaction [Curcumin increases phosphorylation of MAP2K4 protein in uterine cervix]RGD 
N-acetyl-L-cysteine multiple interactionsEXP 150429751N-acetyl-L-cysteine co-treated with Curcumin increases phosphorylation of MAP3K5 protein in uterine cervixRGD 
N-acetyl-L-cysteine multiple interactionsEXP 150429751N-acetyl-L-cysteine inhibits the reaction [Curcumin increases phosphorylation of MAPK8 protein in uterine cervix]RGD 
N-acetyl-L-cysteine multiple interactionsISOMAP2K4 (Homo sapiens)150429751; 150429751N-acetyl-L-cysteine inhibits the reaction [Curcumin increases phosphorylation of MAP2K4 protein in uterine cervix]RGD 
N-acetyl-L-cysteine multiple interactionsISOMAP3K5 (Homo sapiens)150429751; 150429751N-acetyl-L-cysteine co-treated with Curcumin increases phosphorylation of MAP3K5 protein in uterine cervixRGD 
N-acetyl-L-cysteine multiple interactionsISOMAPK8 (Homo sapiens)150429751; 150429751N-acetyl-L-cysteine inhibits the reaction [Curcumin increases phosphorylation of MAPK8 protein in uterine cervix]RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k4  (mitogen activated protein kinase kinase 4)
Map3k5  (mitogen-activated protein kinase kinase kinase 5)
Mapk8  (mitogen-activated protein kinase 8)

Genes (Mus musculus)
Map2k4  (mitogen-activated protein kinase kinase 4)
Map3k5  (mitogen-activated protein kinase kinase kinase 5)
Mapk8  (mitogen-activated protein kinase 8)

Genes (Homo sapiens)
MAP2K4  (mitogen-activated protein kinase kinase 4)
MAP3K5  (mitogen-activated protein kinase kinase kinase 5)
MAPK8  (mitogen-activated protein kinase 8)


Additional Information