Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin

Kasinski, Andrea L.; Du, Yuhong; Thomas, S.; Zhao, Jingquan; Sun, Shi‐Yong; Khuri, Fadlo R.; Wang, Cun‐Yu; Miyake, Shoji; Sun, Aiming; Snyder, James P.; Liotta, Dennis; Fu, Haian

doi:10.1124/mol.108.046201

Cited by 148 publications

(163 citation statements)

References 31 publications

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“…Curcumin is able to suppress NF-κB activation by an Akt-dependent or Akt-independent inhibition of IKK (15,16,45). Certain curcumin analogues, including 3,5-bis(2-flurobenzylidene) piperidin-4-one (EF24) have been found to have a potent inhibitory effect on NF-κB (46). In the present study, we identified that 5 out of 6 cyclohexanone curcumin analogues tested had a more potent inhibitory effect than curcumin on activation of NF-κB in PC-3 cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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Abstract. Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A 1 -A 6 ) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A 2 -A 6 ) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A 2 -A 6 also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A 2 -A 6 using suitable animal models of prostate cancer. IntroductionCurcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Curcumin lacks toxicity in humans (1), and extensive research over several decades has revealed that curcumin possesses anticancer, anti-inflammatory, antioxidant, antiviral and anti-bacterial activities (2,3). Curcumin suppressed cell proliferation or induced apoptosis in cultured prostate cancer cells and other types of cancer cells (4-10). Curcumin also inhibited prostate carcinogenesis (11). Studies from our laboratory and those of other authors have demonstrated enhanced anticancer activities of curcumin when combined with other anticancer agents (12-14). Findings of earlier studies showed that curcumin exerts a wide range of anticancer effects by modulating a diversity of signaling pathways, including nuclear factor-κB (NF-κB) and other pathways (15)(16)(17)(18)(19)(20). Curcumin has entered clinical trials for certain types of human cancer (21-23). However, the clinical efficacy of curcumin is limited, which is likely to be due to its low bioavailability (21-23). It was suggested that the β-diketone moiety of curcumin causes instability and poor metabolic properties (24-26). Enhanced stability was found in curcumin analogues by deleting the β-diketone moiety of the molecule (27). Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells. We also determined the inhibitory effect ...

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Section: Discussionmentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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“…Likewise, curcumin has been shown to inhibit NF-jB activation in ovarian cancer cells [30,36]. In several ovarian cancer cell lines (SKOV3ip1 and HeyA8), curcumin suppressed NF-jB and STAT-3 activation and inhibited expression of COX-2 [36].…”

Section: Curcuminmentioning

confidence: 99%

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

Kim

Han

et al. 2011

Genes Nutr

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Inflammation has been suggested to be involved in cancer development and progression. Many clinical and experimental studies have shown that inflammation could contribute to ovarian carcinogenesis through activation of the NF-jB and AP-1 pathways by chronic inflammatory mediators. Phytochemicals, which are natural compounds derived from fruits and vegetables, have shown anti-inflammatory and anti-cancer effects. Due to their relatively low toxicity and easy accessibility, phytochemicals have been investigated for their chemopreventive potential against various cancers. In this review, we discuss the role of phytochemicals in preventing ovarian cancer through anti-inflammatory mechanisms.

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“…However, treatment with 20 µM curcumin downregulated the constitutively active NF-κB in the REH cell line, both alone and in combination with all the therapeutic agents tested. It is postulated that this downregulation occurs via activation of the inhibitor of kappa B α (24).…”

Section: Discussionmentioning

confidence: 99%

Curcumin potentiates the effect of chemotherapy against acute lymphoblastic leukemia cells via downregulation of NF-κB

et al. 2016

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Abstract. Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin. The results of cell viability, gene expression and activation of NF-κB and caspase 3 indicated that curcumin potentiates the anticancer effects of the aforementioned chemotherapeutic agents in the REH ALL cell line. Following treatment with the above chemotherapeutic agents, curcumin enhanced caspase-3 activation and downregulated nuclear factor-kappa B (NF-κB) activation. Curcumin also downregulated the oxidative stress induced by certain chemotherapies. Notably, curcumin did not affect the gene expression of cell survival proteins such as B-cell lymphoma (Bcl)-2, Bcl-extra large, survivin, c-Myc and cyclin D1, which are regulated by the NF-κB transcription factor. In conclusion, curcumin has the potential to improve the effect of chemotherapeutic agents against ALL.

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Inhibition of IκB Kinase-Nuclear Factor-κB Signaling Pathway by 3,5-Bis(2-flurobenzylidene)piperidin-4-one (EF24), a Novel Monoketone Analog of Curcumin

Cited by 148 publications

References 31 publications

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Modulation of inflammatory signaling pathways by phytochemicals in ovarian cancer

Curcumin potentiates the effect of chemotherapy against acute lymphoblastic leukemia cells via downregulation of NF-κB

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