Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin

Chen, Yi Rong; Tan, Tse Hua

doi:10.1038/sj.onc.1201941

Cited by 363 publications

(193 citation statements)

References 39 publications

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“…The activation of JNK was chemically inhibited by curcumin. Curcumin 20 mm was the lowest concentration that inhibited JNK activation at 24 h, in agreement with prior studies (Chen and Tan, 1998). At this concentration, curcumin also diminished the cleavage of PARP to background levels ( Figure 2a).…”

Section: Taxotere-induced Parp Cleavage Is Mediated Through Jnk Activsupporting

confidence: 79%

“…Blocking JNK activation with a variety of inhibitors reversed Taxotere-induced PARP cleavage. While inhibitors such as curcumin (diferuloylmethane) can inhibit c-Jun and NF-kB, JNK and ERK, the dose that inhibited JNK did not inhibit p38 or ERK, as demonstrated here or previously (Chen and Tan, 1998). The other inhibitors also acted specifically on JNK.…”

Section: Discussionmentioning

confidence: 67%

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All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells

Wang¹,

Wieder²

2004

Oncogene

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Taxotere is a cytotoxin effective in treating breast and prostate cancer. It stabilizes microtubules and causes catastrophic cell cycle arrest in G2/M. Taxanes also initiate apoptosis by activating signal pathways, such as the jun N-terminal kinase (JNK) pathway. Strategies aimed at potentiating cell death signaling may improve their efficacy while lessening the potential side effects. We reported that all-trans retinoic acid (ATRA) potentiated taxane-mediated cell death. Here we investigated whether ATRA potentiates cell death signaling through the JNK pathway. Activation of JNK by Taxotere 0.01, 0.1 and 1.0 lm was observed at 24 h in adherent cells and increased at 48 h. Taxotere 0.001 lm-induced JNK activation started after 48 h and increased at 72 h. The timing and intensity of PARP cleavage was similar to that of JNK activation. JNK activation and PARP cleavage induced by 30 nm Taxotere at 48 h were reversed by curcumin, PD169316 and SP600125, JNK inhibitors in order of progressive specificity. None of these inhibitors had an effect on p38 or ERK phosphorylation. All three inhibitors reversed Taxotere-induced phosphorylation of Bcl-2. ATRA induced JNK activation at 24, 48 and 72 h. Incubating cells with ATRA 0.01 lm for 3 days prior to Taxotere treatment potentiated Taxotere-induced JNK activation 24 and 48 h later, an effect sustained for 72 h. Cytotoxicities from 3-day ATRA 0.01 lm incubations were synergistic with subsequent 1-h Taxotere 0.01, 0.1 and 1.0 lm incubations in breast cancer cell lines MCF-7 and MDA-MB-231 and in prostate cancer cell lines LNCaP and PC-3, and additive in breast cancer cell line SK-Br-3. These data demonstrate the potentiation of Taxotere-induced cell death by ATRA pretreatment in breast and prostate cancer cells, and support a mechanism through accentuated and sustained JNK activation.

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Section: Taxotere-induced Parp Cleavage Is Mediated Through Jnk Activsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 67%

All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells

Wang¹,

Wieder²

2004

Oncogene

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“…Others and we have previously demonstrated that curcumin effectively inhibits the extracellular signalregulated kinase (ERK) in a variety of cells, including colon cancer cells (Chen and Tan, 1998;Chen et al, 1999;Jobin et al, 1999). To determine the role of the ERK signal pathway in curcumin inhibition of the egfr promoter activity, Moser cells were cotransfected with the plasmid pER1-Luc and the cDNA expression plasmid pdn-ERK, or pa-ERK, at indicated doses.…”

Section: Curcumin Inhibits Gene Expression Of Egfr In Human Colon Canmentioning

confidence: 99%

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

2005

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High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and sitedirected mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

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“…The constructs for Flag-PP4 (PPX), GST-Jun(1 ± 79), and Flag-MKK7 were described previously (Chen and Tan, 1998;Hu et al, 1998;Yao et al, 1997).…”

Section: Plasmidsmentioning

confidence: 99%

Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and activation of JNK by hydrogen peroxide and pyrrolidine dithiocarbamate

2001

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Oxidative stress activates the c-Jun N-terminal kinase (JNK) pathway. However, the exact mechanisms by which reactive oxygen species (ROS) activate JNK are unclear. We found that the ability of hydrogen peroxide (H 2 O 2 ) to induce JNK activation varied in di erent cell types. Pyrrolidine dithiocarbamate (PDTC), a presumed antioxidant, induced JNK activation on its own and enhanced JNK activation by H 2 O 2 in many cell types, including Jurkat, HEK293, and LNCaP and Tsu-Pr1 prostate cancer cells. The activation of JNK by PDTC, in the presence or absence of exogenous H 2 O 2 , was dependent on its chelating ability to metal ions, most likely copper ions. Despite the strong JNK-activating ability, H 2 O 2 plus PDTC did not induce signi®cant activation of the upstream kinases, SEK1/MKK4 and MKK7. However, the JNK inactivation rate was slower in cells treated with H 2 O 2 plus PDTC compared with the rate in cells treated with ultraviolet C (UV-C). Treatment of H 2 O 2 plus PDTC signi®cantly decreased the expression levels of a JNK phosphatase, M3/6 (also named hVH-5), but not the levels of other phosphatases (PP2A and PP4). In contrast, UV-C irradiation did not cause the down-regulation of M3/6. These results suggest that JNK activation by H 2 O 2 plus PDTC resulted from the down-regulation of JNK phosphatases. Our data also reveal a necessity to carefully evaluate the pharmacological and biochemical properties of PDTC. Oncogene (2001) 20, 367 ± 374.

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Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin

Cited by 363 publications

References 39 publications

All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells

All-trans retinoic acid potentiates Taxotere-induced cell death mediated by Jun N-terminal kinase in breast cancer cells

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

Down-regulation of the c-Jun N-terminal kinase (JNK) phosphatase M3/6 and activation of JNK by hydrogen peroxide and pyrrolidine dithiocarbamate

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