Activation of Transcription Factor NF-κB Is Suppressed by Curcumin (Diferuloylmethane)

Singh, Sanjaya; Aggarwal, Bharat B.

doi:10.1074/jbc.270.42.24995

Cited by 1,279 publications

(941 citation statements)

References 45 publications

(40 reference statements)

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“…Curcumin is a dietary compound with the known properties of antioxidation, anti-in¯ammation, and anticarcinogenesis (Huang et al, 1994;1988;Rao et al, 1995;Ruby et al, 1995;Singh and Aggarwal, 1995). Curcumin blocks c-jun expression and NF-kB activation induced by various agents (Hanazawa et al, 1993;Huang et al, 1991;Singh and Aggarwal, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The anticarcinogenic e ects of this compound are demonstrated by its ability to inhibit tumor initiation by azoxymethane, benzpyrene and 7,12-dimethyl-benz(a)anthracene, and to suppress tumor promotion by phorbol esters (Huang et al, 1994(Huang et al, , 1988Rao et al, 1995). It has been shown that curcumin strongly inhibits both c-Jun and NF-kB activation by PMA or tumor necrosis factor-a (TNF-a) treatments (Hanazawa et al, 1993;Huang et al, 1991;Singh and Aggarwal, 1995). This inhibitory e ect may account for the anti-in¯ammatory and anti-oxidant properties of curcumin (Ruby et al, 1995;Singh and Aggarwal, 1995); however, the mechanism of these inhibitory e ects remains unclear.…”

mentioning

confidence: 99%

“…It has been shown that curcumin strongly inhibits both c-Jun and NF-kB activation by PMA or tumor necrosis factor-a (TNF-a) treatments (Hanazawa et al, 1993;Huang et al, 1991;Singh and Aggarwal, 1995). This inhibitory e ect may account for the anti-in¯ammatory and anti-oxidant properties of curcumin (Ruby et al, 1995;Singh and Aggarwal, 1995); however, the mechanism of these inhibitory e ects remains unclear. In the present report, we show that curcumin completely blocked JNK activation by various agents including PMA plus ionomycin, g radiation, UV-C, anisomycin, TNF-a, and sodium orthovanadate.…”

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confidence: 99%

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

1998

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Curcumin, a dietary pigment in curry, suppresses tumor initiation and tumor promotion. Curcumin is also a potent inhibitor for AP-1 and NF-kB activation. In this report, we show that curcumin inhibits JNK activation by various agonists including PMA plus ionomycin, anisomycin, UV-C, g radiation, TNF-a, 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 IC 50 (50% inhibition concentration) of curcumin was between 5 ± 10 mM for JNK activation and was 20 mM for ERK activation. In transfection assays, curcumin moderately suppressed MEKK1-induced JNK activation; however, it e ectively 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 a ect 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-kB signaling by curcumin, and may explain the potent anti-in¯ammatory and anti-carcinogenic e ects of this chemical.

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Section: Discussionmentioning

confidence: 99%

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

1998

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“…In studies of the myeloid cell line ML-1a, Singh and Aggarwal reported that curcumin inhibited IkBa phosphorylation, degradation, and NF-kB translocation induced by a diverse range of stimuli including TNF, hydrogen peroxide, and phorbol esters [2]. Subsequent studies confirmed curcumininduced inhibition of NF-kB translocation in multiple cell types, including colon [3], gastric [4], pancreatic [5], and squamous epithelial tumor cell lines [6] as well as B-cell lymphoma and multiple myeloma cell lines [7,8].…”

Section: Introductionmentioning

confidence: 99%

Preclinical assessment of curcumin as a potential therapy for B‐CLL

et al. 2006

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Curcumin, the principle component of the spice turmeric, has been used as an anti-inflammatory medication in India and China for centuries. Recent studies, predominantly using actively dividing cell lines, have suggested that this compound could be used as a chemopreventative or therapeutic agent for epithelial tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity that would be expected to induce apoptosis in B cell malignancies, we sought to determine whether curcumin induces apoptosis in vitro in primary chronic lymphocytic leukemia (B-CLL) cells. Primary leukemic cells were incubated with varying dosages of curcumin, followed by assessment for apoptosis. The role of PPARg or NF-kB signaling in curcumin-induced apoptosis was examined by cotreatment with a PPARg antagonist or EMSA of nuclear NFkB complexes. We also examined whether a clinically achievable concentration of curcumin (1 mM) would augment the apoptotic effects of fludarabine, dexamethasone, vincristine or the PDE4 inhibitor rolipram. In B-CLL cells from 14 patients, curcumin-induced apoptosis with a mean EC 50 of 5.5 mM. In contrast, the EC 50 for whole mononuclear cells from a healthy donor was 21.8 mM. In a 48 hr wash-out time course, curcumin-induced apoptosis was time-dependent, with a substantial reduction in apoptosis observed when curcumin was removed after 5 hr. Curcumin treatment reduced basal nuclear NF-kB levels and 1 mM curcumin augmented both vinca alkaloid and PDE4 inhibitor-induced apoptosis in B-CLL cells. Our studies suggest that curcumin may augment the efficacy of established or experimental therapies for B-CLL. Am. J. Hematol. 82:23-30, 2007. V V C 2006 Wiley-Liss, Inc.

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“…[15][16][17][18] In addition, synthetic double-stranded DNA (dsDNA) with high affinity for NFkB, NFkB decoy, have been shown to block the induction of gene expression mediated by NFkB in vitro 15,[19][20][21][22] and in vivo. 23,24 With the use of decoy oligonucleotides, the function of a particular DNA-binding protein or protein complex can be inhibited since the decoy competes for protein binding with the authentic binding elements, interfering with gene regulation.…”

Section: Introductionmentioning

confidence: 99%

Cellular delivery of a double-stranded oligonucleotide

et al. 2004

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The activation of nuclear factor kB (NFkB) is a key event in immune and inflammatory responses. In this study, a cellpenetrating transport peptide, transportan (TP) or its shorter analogue TP 10, was used to facilitate the cellular uptake of an NFkB decoy. Peptide nucleic acid (PNA) hexamer or nonamer was linked to the transport peptide by a disulfide bond. NFkB decoy oligonucleotide consisted of a doublestranded consensus sequence corresponding to the kB site localized in the IL-6 gene promoter, 5 0 -GGGACTTTCCC-3 0 , with a single-stranded protruding 3 0 -terminal sequence complementary to the PNA sequence was hybridized to the transport peptide-PNA construct. The ability of the transport peptide-PNA-NFkB decoy complex to block the effect of interleukin (IL)-1b-induced NFkB activation and IL-6 gene expression was analyzed by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction in rat Rinm5F insulinoma cells. Preincubation with transport peptide-PNA-NFkB decoy (1 mM, 1 h) blocked IL-1b-induced NFkB-binding activity and significantly reduced the IL-6 mRNA expression. The same concentration of NFkB decoy in the absence of transport peptide-PNA had no effect even after longer incubations. Our results showed that binding of the oligonucleotide NFkB decoy to the nonamer PNA sequence resulted in a stable complex that was efficiently translocated across the plasma membrane.

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Activation of Transcription Factor NF-κB Is Suppressed by Curcumin (Diferuloylmethane)

Cited by 1,279 publications

References 45 publications

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

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

Preclinical assessment of curcumin as a potential therapy for B‐CLL

Cellular delivery of a double-stranded oligonucleotide

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