3-Formylchromone Interacts with Cysteine 38 in p65 Protein and with Cysteine 179 in IκBα Kinase, Leading to Down-regulation of Nuclear Factor-κB (NF-κB)-regulated Gene Products and Sensitization of Tumor Cells

Yadav, Vivek R.; Prasad, Sahdeo; Gupta, Subash C.; Sung, Bokyung; Phatak, Sharangdhar S.; Zhang, Shuxing; Aggarwal, Bharat B.

doi:10.1074/jbc.m111.274613

Cited by 19 publications

(8 citation statements)

References 38 publications

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“…NF-κB family members form two dimers with homologous or heterologous forms, the most common dimer being the combination of p50 and p65. NF-κB is formed by the heterologous dimerization of p50 and p65, and NF-κB p65 acts an important nucleus transcription factor [31,34]. …”

Section: Discussionmentioning

confidence: 99%

Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

et al. 2013

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BackgroundHigh mobility group protein box 1 (HMGB1) is a DNA binding protein located in nucleus. It is released into extracellular fluid where it acts as a novel proinflammatory cytokine which interacts with Toll like receptor 4 (TLR4) to activate nuclear factor-κB (NF-κB). This sequence of events is involved in tumor growth and progression. However, the effects of HMGB1, TLR4 and NF-κB on epidermal tumors remain unclear.MethodsHuman epidermal tumor specimens were obtained from 96 patients. Immunohistochemistry was used to detect expression of HMGB1, TLR4 and NF-κB p65 in human epidermal tumor and normal skin specimens. Western blot analysis was used to detect the expression of NF-κB p65 in epithelial cell nuclei in human epidermal tumor and normal tissues.ResultsImmunohistochemistry and western blot analysis indicated a progressive but statistically significant increase in p65 expression in epithelial nuclei in benign seborrheic keratosis (SK), precancerous lesions (PCL), low malignancy basal cell carcinoma (BCC) and high malignancy squamous cell carcinoma (SCC) (P <0.01). The level of extracellular HMGB1 in SK was significantly higher than in normal skin (NS) (P <0.01), and was higher than in SCC but without statistical significance. The level of TLR4 on epithelial membranes of SCC cells was significantly higher than in SK, PCL, BCC and NS (P <0.01). There was a significant positive correlation between p65 expression in the epithelial nuclei and TLR4 expression on the epithelial cell membranes (r = 0.3212, P <0.01).ConclusionsThese findings indicate that inflammation is intensified in parallel with increasing malignancy. They also indicate that the TLR4 signaling pathway, rather than HMGB1, may be the principal mediator of inflammation in high-grade malignant epidermal tumors. Combined detection of p65 in the epithelial nuclei and TLR4 on the epithelial membranes may assist the accurate diagnosis of malignant epidermal tumors.

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Section: Discussionmentioning

confidence: 99%

Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

et al. 2013

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“…Therefore, ROS released by TA may affect NF-jB directly through crosstalk with p65 and its modification [42]. In fact, ROS-mediated modification of cysteine residues in p65 and IKK modulates NF-jB activation [43,44]. Complete inhibition in TA-induced apoptosis by NAC treatment highlights the possibly pleiotropic mechanisms of ROS-dependent apoptosis by TA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species mediate tolfenamic acid-induced apoptosis in human colorectal cancer cells

Jeong

Choi

Baek

et al. 2013

Archives of Biochemistry and Biophysics

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“…It has been shown that the cysteine residue located at position 38 in p65 is highly susceptible to various agents [13]. To investigate whether piperlongumine could bind directly to Cys38 of p65, we performed a mass spectrometry analysis of a synthetic p65 peptide.…”

Section: Piperlongumine Directly Binds To Cysteine 38 Of Nf-kb P65 Sumentioning

confidence: 99%

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

Niu

Shen

et al. 2015

Biochemical and Biophysical Research Communications

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3-Formylchromone Interacts with Cysteine 38 in p65 Protein and with Cysteine 179 in IκBα Kinase, Leading to Down-regulation of Nuclear Factor-κB (NF-κB)-regulated Gene Products and Sensitization of Tumor Cells

Cited by 19 publications

References 38 publications

Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors

Reactive oxygen species mediate tolfenamic acid-induced apoptosis in human colorectal cancer cells

Piperlongumine selectively suppresses ABC-DLBCL through inhibition of NF-κB p65 subunit nuclear import

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