Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis.

@article{Anand2008ModificationOC,
  title={Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis.},
  author={Preetha Anand and Ajaikumar B. Kunnumakkara and Kuzhuvelil B Harikumar and Kwang Seok Ahn and Vladimir Badmaev and Bharat Bhushan Aggarwal},
  journal={Cancer research},
  year={2008},
  volume={68 21},
  pages={
          8861-70
        }
}
Picroliv, an iridoid glycoside derived from the plant Picrorhiza kurroa, is used traditionally to treat fever, asthma, hepatitis, and other inflammatory conditions. However, the exact mechanism of its therapeutic action is still unknown. Because nuclear factor-kappaB (NF-kappaB) activation plays a major role in inflammation and carcinogenesis, we postulated that picroliv must interfere with this pathway by inhibiting the activation of NF-kappaB-mediated signal cascade. Electrophoretic mobility… 

Figures from this paper

NF-κB addiction and its role in cancer: ‘one size does not fit all’

Multiple mechanisms of NF-κB activation and their regulation by multitargeted agent in contrast to monotargeted agents are discussed, thus ‘one size does not fit all’ cancers.

Retraction: Modification of Cysteine Residue in p65 Subunit of Nuclear Factor-κB (NF-κB) by Picroliv Suppresses NF-κB-Regulated Gene Products and Potentiates Apoptosis.

  • Biology
    Cancer research
  • 2018
This article (1) has been retracted at the request of the editors. An institutional investigation determined that the sameNF-kBEMSA imagewas used to represent two different experimental conditions in

Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway

Evidence is provided for a strong effect of the neem extract on pro-inflammatory cell signaling and apoptotic cell death mechanisms, contributing to a better understanding of the mechanisms triggered by Azadirachta indica.

Dimethyl Fumarate Inhibits the Nuclear Factor κB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein*

DMF is established as an NFκB inhibitor with anti-tumor activity that may add therapeutic value in the treatment of aggressive breast cancers and has anti-cancer stem cell properties.

Anti-NFκB activity of DMF in breast cancer cells 1 Dimethyl Fumarate Inhibits the Nuclear Factor κB Pathway in Breast Cancer Cells by Covalent Modification of p65*

DMF is established as an NFκB inhibitor with anti-tumor activity that may add therapeutic value in treating aggressive breast cancers and is shown to have anti-cancer stem cells properties.

Plant derived inhibitors of NF-κB

Plant-derived phytochemicals are promising lead compounds to develop potent and safe inhibitors for cancer and inflammatory disorders driven by NF-κB.
...

References

SHOWING 1-10 OF 52 REFERENCES

Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-kappaB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis.

It is demonstrated that gossypin inhibits the NF-kappaB activation pathway, which may explain its role in the suppression of inflammation, carcinogenesis, and angiogenesis.

Cigarette smoke condensate activates nuclear transcription factor-κB through phosphorylation and degradation of IκBα: correlation with induction of cyclooxygenase-2

The results indicate that through phosphorylation and degradation of IkappaB(alpha), CSC can activate NF-kappaB in a wide a variety of cells, and this may play a role in CS-induced carcinogenesis.

Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

The results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.

Cysteine 38 in p65/NF-κB Plays a Crucial Role in DNA Binding Inhibition by Sesquiterpene Lactones*

Contrary to previous reports, it is shown that parthenolide, like other SLs, inhibits NF-κB most probably by alkylating p65 at Cys38, and the amount of remaining IκB was too low to explain the observed NF-β degradation inhibition.

Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses NF-κB Activation and NF-κB-regulated Gene Products Through Modulation of p65 and IκBα Kinase Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents*

It is found that plumbagin inhibited NF-κB activation induced by TNF, and other carcinogens and inflammatory stimuli (e.g. phorbol 12-myristate 13-acetate, H2O2, cigarette smoke condensate, interleukin-1β, lipopolysaccharide, and okadaic acid).

Hydrogen Peroxide Activates NF-κB through Tyrosine Phosphorylation of IκBα and Serine Phosphorylation of p65

The results demonstrate that H2O2 induces NF-κB activation, not through serine phosphorylation or degradation of IκBα, but through Syk-mediated tyrosineosphorylation of IσBα.

Studies into the Effect of the Tyrosine Kinase Inhibitor Herbimycin A on NF-κB Activation in T Lymphocytes EVIDENCE FOR COVALENT MODIFICATION OF THE p50 SUBUNIT (*)

The results urge caution in the use of herbimycin A as a specific tyrosine kinase inhibitor and suggest that the development of agents that selectively modify p50 may have potential as a means of inhibiting NF-κB-dependent gene transcription.

Nuclear transcription factor-kappaB as a target for cancer drug development.

The current knowledge of NF-kappaB, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF- kappaB signaling pathway for cancer drug development are reviewed.
...