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Morin (3,5,7,2',4'-Pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis.
Clin Cancer Res. 2007 Apr 01; 13(7):2290-7.CC

Abstract

PURPOSE

Morin is a flavone that exhibits antiproliferative, antitumor, and anti-inflammatory effects through a mechanism that is not well understood. Because of the role of transcription factor nuclear factor-kappaB (NF-kappaB) in the control of cell survival, proliferation, tumorigenesis, and inflammation, we postulated that morin mediates its effects by modulating NF-kappaB activation.

EXPERIMENTAL DESIGN

We investigated the effect of morin on NF-kappaB pathway activated by inflammatory agents, carcinogens, and tumor promoters. The effect of this flavone on expression of NF-kappaB-regulated gene products involved in cell survival, proliferation, and invasion was also examined.

RESULTS

We showed by DNA-binding assay that NF-kappaB activation induced by tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, lipopolysaccharide, ceramide, interleukin-1, and H(2)O(2) was suppressed by morin; the suppression was not cell type specific. The suppression of NF-kappaB by morin was mediated through inhibition of IkappaBalpha (inhibitory subunit of NF-kappaB) kinase, leading to suppression of phosphorylation and degradation of IkappaBalpha and consequent p65 nuclear translocation. Morin also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR1-associated death domain, TNFR-associated factor 2, NF-kappaB-inducing kinase, IkappaB kinase, and the p65 subunit of NF-kappaB. NF-kappaB-regulated gene products involved in cell survival [inhibitor of apoptosis (IAP) 1, IAP2, X chromosome-linked IAP, Bcl-xL, and survivin], proliferation (cyclin D1 and cyclooxygenase-2), and invasion (matrix metalloproteinase-9) were down-regulated by morin. These effects correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents.

CONCLUSION

Overall, our results indicate that morin suppresses the activation of NF-kappaB and NF-kappaB-regulated gene expression, leading to enhancement of apoptosis. This may provide the molecular basis for the ability of morin to act as an anticancer and anti-inflammatory agent.

Authors+Show Affiliations

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Cente, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17404114

Citation

Manna, Sunil K., et al. "Morin (3,5,7,2',4'-Pentahydroxyflavone) Abolishes Nuclear factor-kappaB Activation Induced By Various Carcinogens and Inflammatory Stimuli, Leading to Suppression of Nuclear factor-kappaB-regulated Gene Expression and Up-regulation of Apoptosis." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 13, no. 7, 2007, pp. 2290-7.
Manna SK, Aggarwal RS, Sethi G, et al. Morin (3,5,7,2',4'-Pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res. 2007;13(7):2290-7.
Manna, S. K., Aggarwal, R. S., Sethi, G., Aggarwal, B. B., & Ramesh, G. T. (2007). Morin (3,5,7,2',4'-Pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 13(7), 2290-7.
Manna SK, et al. Morin (3,5,7,2',4'-Pentahydroxyflavone) Abolishes Nuclear factor-kappaB Activation Induced By Various Carcinogens and Inflammatory Stimuli, Leading to Suppression of Nuclear factor-kappaB-regulated Gene Expression and Up-regulation of Apoptosis. Clin Cancer Res. 2007 Apr 1;13(7):2290-7. PubMed PMID: 17404114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Morin (3,5,7,2',4'-Pentahydroxyflavone) abolishes nuclear factor-kappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. AU - Manna,Sunil K, AU - Aggarwal,Rishi S, AU - Sethi,Gautam, AU - Aggarwal,Bharat B, AU - Ramesh,Govindarajan T, PY - 2007/4/4/pubmed PY - 2007/6/22/medline PY - 2007/4/4/entrez SP - 2290 EP - 7 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 13 IS - 7 N2 - PURPOSE: Morin is a flavone that exhibits antiproliferative, antitumor, and anti-inflammatory effects through a mechanism that is not well understood. Because of the role of transcription factor nuclear factor-kappaB (NF-kappaB) in the control of cell survival, proliferation, tumorigenesis, and inflammation, we postulated that morin mediates its effects by modulating NF-kappaB activation. EXPERIMENTAL DESIGN: We investigated the effect of morin on NF-kappaB pathway activated by inflammatory agents, carcinogens, and tumor promoters. The effect of this flavone on expression of NF-kappaB-regulated gene products involved in cell survival, proliferation, and invasion was also examined. RESULTS: We showed by DNA-binding assay that NF-kappaB activation induced by tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, lipopolysaccharide, ceramide, interleukin-1, and H(2)O(2) was suppressed by morin; the suppression was not cell type specific. The suppression of NF-kappaB by morin was mediated through inhibition of IkappaBalpha (inhibitory subunit of NF-kappaB) kinase, leading to suppression of phosphorylation and degradation of IkappaBalpha and consequent p65 nuclear translocation. Morin also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR1-associated death domain, TNFR-associated factor 2, NF-kappaB-inducing kinase, IkappaB kinase, and the p65 subunit of NF-kappaB. NF-kappaB-regulated gene products involved in cell survival [inhibitor of apoptosis (IAP) 1, IAP2, X chromosome-linked IAP, Bcl-xL, and survivin], proliferation (cyclin D1 and cyclooxygenase-2), and invasion (matrix metalloproteinase-9) were down-regulated by morin. These effects correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. CONCLUSION: Overall, our results indicate that morin suppresses the activation of NF-kappaB and NF-kappaB-regulated gene expression, leading to enhancement of apoptosis. This may provide the molecular basis for the ability of morin to act as an anticancer and anti-inflammatory agent. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/17404114/Morin__3572'4'_Pentahydroxyflavone__abolishes_nuclear_factor_kappaB_activation_induced_by_various_carcinogens_and_inflammatory_stimuli_leading_to_suppression_of_nuclear_factor_kappaB_regulated_gene_expression_and_up_regulation_of_apoptosis_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17404114 DB - PRIME DP - Unbound Medicine ER -