Inhibition of NF-κB Sensitizes A431 Cells to Epidermal Growth Factor-induced Apoptosis, whereas Its Activation by Ectopic Expression of RelA Confers Resistance

Anto, Ruby John; Manickam, Venkatraman; Karunagaran, Devarajan

doi:10.1074/jbc.m301790200

Cited by 60 publications

(45 citation statements)

References 59 publications

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“…Cyclin D1, which is overexpressed in a variety of tumors , is regulated by NF-B (Guttridge et al, 1999) and is required for cells to advance from the G 1 phase to the S phase of the cell cycle (Weinstein, 2000). That curcumin down-regulates cyclin D1 expression may explain the results from earlier reports indicating that this agent induces G 1 /S arrest (Anto et al, 2003;Schnaeker et al, 2004). It also may explain the antiproliferative effects of curcumin.…”

Section: Discussionsupporting

confidence: 67%

Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation

et al. 2005

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Curcumin (diferuloylmethane), an anti-inflammatory agent used in traditional medicine, has been shown to suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis through a mechanism not fully understood. Because several genes that mediate these processes are regulated by nuclear factor-B (NF-B), we have postulated that curcumin mediates its activity by modulating NF-B activation. Indeed, our laboratory has shown previously that curcumin can suppress NF-B activation induced by a variety of agents (J Biol Chem 270:24995-50000, 1995) . In the present study, we investigated the mechanism by which curcumin manifests its effect on NF-B and NF-B-regulated gene expression. Screening of 20 different analogs of curcumin showed that curcumin was the most potent analog in suppressing the tumor necrosis factor (TNF)-induced NF-B activation. Curcumin inhibited TNF-induced NF-B-dependent reporter gene expression in a dose-dependent manner. Curcumin also suppressed NF-B reporter activity induced by tumor necrosis factor receptor (TNFR)1, TNFR2, NF-B-inducing kinase, IB kinase complex (IKK), and the p65 subunit of NF-B. Such TNFinduced NF-B-regulated gene products involved in cellular proliferation [cyclooxygenase-2 (COX-2), cyclin D1, and c-myc], antiapoptosis [inhibitor of apoptosis protein (IAP)1, IAP2, X-chromosome-linked IAP, Bcl-2, Bcl-x L , Bfl-1/A1, TNF receptor-associated factor 1, and cellular Fas-associated death domain protein-like interleukin-1␤-converting enzyme inhibitory protein-like inhibitory protein], and metastasis (vascular endothelial growth factor, matrix metalloproteinase-9, and intercellular adhesion molecule-1) were also down-regulated by curcumin. COX-2 promoter activity induced by TNF was abrogated by curcumin. We found that curcumin suppressed TNFinduced nuclear translocation of p65, which corresponded with the sequential suppression of IB␣ kinase activity, IB␣ phosphorylation, IB␣ degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acetylation. Curcumin also inhibited TNF-induced Akt activation and its association with IKK. Glutathione and dithiothreitol reversed the effect of curcumin on TNF-induced NF-B activation. Overall, our results indicated that curcumin inhibits NF-B activation and NF-B-regulated gene expression through inhibition of IKK and Akt activation.It is generally assumed that traditional medicines are safe and efficacious, given that they have been used for centuries. Despite the widespread use of these medicines, however, research to definitively establish safety and efficacy of many of them is lacking. Between 1981 and 2002, almost 74% (48 of 65) of all drugs approved for cancer were either natural products or based on natural products (typically, analogs or mimics) (Newman et al., 2003). The delineation of their Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.doi:10.1124/mol.105.017400. ABBREVIATIONS:COX-2, cyclooxygenase-2; MMP, matrix metalloproteinase; TNF, tumor necro...

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Section: Discussionsupporting

confidence: 67%

Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation

et al. 2005

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“…Inhibition of NF-kB with IkB-SR has previously been shown to sensitize A431 cells to EGF-induced apoptosis (Anto et al, 2003). In our study, however, we were unable to detect A431 cell apoptosis or caspase activity in response to NF-kB inhibition by IkB-SR or ABIN-1 overexpression, indicating that the reduced cell number mainly reflects an effect on cell proliferation.…”

Section: Inhibition Of Egfr-induced Signalling By Abinscontrasting

confidence: 52%

ABINs inhibit EGF receptor-mediated NF-κB activation and growth of EGF receptor-overexpressing tumour cells

et al. 2008

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“…After 72 h of exposure, viability was assessed on the basis of cellular conversion of MTT into a formazan product using the Promega CellTiter 96 Non-radioactive Cell Proliferation Assay (Anto et al, 2003). Briefly, 20 ml of MTT solution (5 mg/mL phosphate-buffered saline) were added to each well.…”

Section: Determination Of Cytotoxicity Of Dkps In Vero Cellsmentioning

confidence: 99%

Antimycobacterial activity of cyclic dipeptides isolated fromBacillussp. N strain associated with entomopathogenic nematode

Kumar

Mohandas

2013

Pharmaceutical Biology

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Context: Tuberculosis (TB) is one of the leading causes of morbidity and mortality with a global mortality rate of two million deaths per year; one-third of the world's population is infected with Mycobacterium tuberculosis. Objective: The aim of this study was to determine the antimycobacterial activity of six diketopiperazines (DKPs) purified from a Bacillus sp. N strain associated with entomopathogenic nematode Rhabditis (Oscheius) sp. Materials and methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of DKPs were determined using the broth dilution method on Middlebrook 7H11 against M. tuberculosis H 37 Rv. Time-kill assay was used to determine the rate of killing of M. tuberculosis H 37 Rv by DKPs. The cytotoxicity of the DKPs was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay against the VERO cell line. Results: Out of six DKP-tested cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe)recorded antimycobacterial activity, the cyclo-(L-Pro-L-Met) showed the highest activity and MIC values of 4 mg/ml for M. tuberculosis H 37 Rv. The MIC value for rifampicin was 0.06 mg/ml. Growth curve study by the MIC concentration of cyclic dipeptides recorded significant inhibition when compared with control. Time-kill curve showed maximum reduction of colony count was between 3 and 5 weeks. The DKPs are nontoxic to the VERO cell line up to 200 mg/ml. The antimycobacterial activity of cyclo-(D-Pro-L-Leu), cyclo-(L-Pro-L-Met) and cyclo-(D-Pro-L-Phe) is reported in this study for the first time. Discussion and conclusion: In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for treatment against TB.

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Inhibition of NF-κB Sensitizes A431 Cells to Epidermal Growth Factor-induced Apoptosis, whereas Its Activation by Ectopic Expression of RelA Confers Resistance

Cited by 60 publications

References 59 publications

Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation

Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of IκBα Kinase and Akt Activation

ABINs inhibit EGF receptor-mediated NF-κB activation and growth of EGF receptor-overexpressing tumour cells

Antimycobacterial activity of cyclic dipeptides isolated fromBacillussp. N strain associated with entomopathogenic nematode

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