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Inhibition of the NF-?B signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

ABSTRACT: Nuclear factor kappa B (NF-?B) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-?B inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogs with enhanced activity on NF-?B and other inflammatory signaling pathways have been developed including the synthetic monoketone compound 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31) is a structurally-related curcumin analog whose potency for NF-?B inhibition has yet to be determined. To examine the activity of EF31 compared to EF24 and curcumin, mouse RAW264.7 macrophages were treated with EF31, EF24, curcumin (1-100 ?M) or vehicle (DMSO 1%) for 1h. NF-?B pathway activity was assessed following treatment with lipopolysaccharide (LPS) (1 ?g/mL). EF31 (IC(50)~5 ?M) exhibited significantly more potent inhibition of LPS-induced NF-?B DNA binding compared to both EF24 (IC(50)~35 ?M) and curcumin (IC(50) >50 ?M). In addition, EF31 exhibited greater inhibition of NF-?B nuclear translocation as well as the induction of downstream inflammatory mediators including pro-inflammatory cytokine mRNA and protein (tumor necrosis factor-?, interleukin-1?, and interleukin-6). Regarding the mechanism of these effects on NF-?B, EF31 (IC(50)~1.92 ?M) exhibited significantly greater inhibition of I?B kinase ? compared to EF24 (IC(50)~131 ?M). Finally, EF31 demonstrated potent toxicity in NF-?B-dependent cancer cell lines while having minimal and reversible toxicity in RAW264.7 macrophages. These data indicate that EF31 is a more potent inhibitor of NF-?B activity than either EF24 or curcumin while exhibiting both anti-inflammatory and anticancer activities. Thus, EF31 represents a promising curcumin analog for further therapeutic development.

SUBMITTER: Olivera A

PROVIDER: S-EPMC3372981 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

Olivera Anlys A Moore Terry W TW Hu Fang F Brown Andrew P AP Sun Aiming A Liotta Dennis C DC Snyder James P JP Yoon Younghyoun Y Shim Hyunsuk H Marcus Adam I AI Miller Andrew H AH Pace Thaddeus W W TW

International immunopharmacology 20111222 2

Nuclear factor kappa B (NF-κB) is a key signaling molecule in the elaboration of the inflammatory response. Data indicate that curcumin, a natural ingredient of the curry spice turmeric, acts as a NF-κB inhibitor and exhibits both anti-inflammatory and anti-cancer properties. Curcumin analogs with enhanced activity on NF-κB and other inflammatory signaling pathways have been developed including the synthetic monoketone compound 3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24). 3,5-Bis(2-pyridiny ...[more]

PMID: 22197802

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Dataset Information

Inhibition of the NF-?B signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

Publications

Inhibition of the NF-κB signaling pathway by the curcumin analog, 3,5-Bis(2-pyridinylmethylidene)-4-piperidone (EF31): anti-inflammatory and anti-cancer properties.

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