Disease relevance of curcumin

• CONCLUSIONS: This study has shown for the first time that treatment with curcumin can prevent and improve murine experimental colitis [1].
• The aim of this study was to determine whether treatment with curcumin prevents and ameliorates colonic inflammation in a mouse model of inflammatory bowel disease [1].
• We report that topotecan, beta-lapachone, and curcumin are potent and selective inhibitors of HIV-1 LTR-directed gene expression, at concentrations that have minor effects on cells [2].
• Our findings suggest that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and may potentially have a therapeutic role in treating selected forms of inherited peripheral neuropathies [3].
• Because of the central role of the transcription factor nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane), an agent known to have very little or no toxicity in humans [4].

Psychiatry related information on curcumin

• In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Abeta deposits [5].
• The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R [6].
• Recently, curcumin has been reported to suppress the amyloid-beta accumulation, oxidative damage, and inflammation in the transgenic mice model of Alzheimer's disease [7].
• A dietary modification with the introduction of soy products, curcumin, cruciferous vegetables and low fat could be beneficial in reducing the risk of developing cancer and possibly the effects of DDT [8].

High impact information on curcumin

• Curcumin treatment in deltaF508-CFTR mice partially reversed the defect in ATP sensitivity [9].
• Dietary curcumin and anti-TNF-alpha antibody counteracted the detrimental effect of TNBS on Phex gene expression [10].
• Consistent with these findings, CD4(+) T-cell infiltration and NF-kappaB activation in colonic mucosa were suppressed in the curcumin-treated group [1].
• METHODS: Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis were treated with 0.5%, 2.0%, or 5.0% curcumin in the diet, and changes in body weight together with histologic scores were evaluated [1].
• In HeLa and MCF-7 cells, inhibition of CSN kinase by curcumin or Deltap53(145-164) results in accumulation of endogenous p53 [11].

Chemical compound and disease context of curcumin

• Earlier studies using prostate cancer cells in culture showed that phenethyl isothiocyanate (PEITC) and curcumin have significant chemopreventive and possibly chemotherapeutic effects [12].
• In the present study, topical application of curcumin markedly inhibited TPA- and arachidonic acid-induced epidermal inflammation (ear edema) in mice, but chlorogenic acid, caffeic acid, and ferulic acid were only weakly active or inactive [13].
• Using an in vivo model of human breast cancer, dietary supplementation with curcumin was found to significantly inhibit cyclophosphamide-induced tumor regression [14].
• The butyrate response was also compared in detail with that of sulindac, a nonsteroidal anti-inflammatory drug with significant chemopreventive activity for colon cancer, and curcumin, a component of mustard and curry structurally and functionally related to sulindac that also has chemopreventive activity [15].
• The results of our studies and those of others provide a rationale for clinical trials on the potential chemopreventive effects of curcumin, caffeine, EGCG, and tea on the formation of cancer of the skin, mouth, esophagus, stomach, and colon in people with precancerous lesions and a high risk of developing these cancers [16].

Biological context of curcumin

• Curcumin suppressed the constitutive IkappaBalpha phosphorylation through the inhibition of IKK activity [4].
• The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1 [17].
• The use of three inhibitors of ERalpha degradation that target different steps of the estrogen response pathway (inhibition of the CSN-associated kinase, nuclear export, and proteasome) suggests that a phosphorylation event inhibited by curcumin is necessary for ERalpha binding to its cognate DNA target [18].
• As regards cell cycle arrest, the underlying mechanism in response to butyrate was most similar to that of the Caco-2 cell line that had spontaneously undergone a G0-G1 arrest and least similar to the G2-M arrest stimulated by curcumin [15].
• Further investigations suggest that neutralization of tumor-induced oxidative stress and restoration of NF-kappaB activity along with the reeducation of the TNF-alpha signaling pathway can be the mechanism behind curcumin-mediated thymic protection [19].

Anatomical context of curcumin

• METHODS: Phex gene expression was evaluated in calvaria of 6-7-week-old mice administered with trinitrobenzene sulfonic acid (TNBS) with or without neutralizing anti-TNF-alpha antibody, dietary curcumin, or systemically with recombinant TNF-alpha [10].
• Curcumin, a CSN kinase inhibitor, blocks E6-dependent p53 degradation in reticulocyte lysates [11].
• Suppression of the c-Jun/AP-1 activation by curcumin is observed in mouse fibroblast cells [20].
• Curcumin treatment abrogates endoplasmic reticulum retention and aggregation-induced apoptosis associated with neuropathy-causing myelin protein zero-truncating mutants [3].
• We found that NF-kappaB was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, down-regulated NF-kappaB in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry [4].

Associations of curcumin with other chemical compounds

• Here, we show that curcumin, a natural phenolic compound found in the spice turmeric, induced ubiquitin-independent degradation of WT p53 and inhibited p53-induced apoptosis in normal thymocytes and myeloid leukemic cells [21].
• Like dicoumarol, curcumin inhibited the activity of recombinant NQO1 in vitro, inhibited the activity of endogenous cellular NQO1 in vivo, and dissociated NQO1-WT p53 complexes [21].
• When compared with curcumin, dexamethasone was less effective in suppression of NF-kappaB activation and induction of apoptosis in myeloma cells [22].
• In addition, we observed that curcumin inhibited estradiol-induced phosphorylation of ERalpha [18].
• The metabolism of arachidonic acid to prostaglandin E2, prostaglandin F2 alpha, and prostaglandin D2 by epidermal microsomes was inhibited approximately 50% by the in vitro addition of 5-10 microM curcumin [13].

Gene context of curcumin

• The results indicate that curcumin induces p53 degradation and inhibits p53-induced apoptosis by an NQO1-dependent pathway [21].
• Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75% [23].
• Results of our metabolism studies showed that curcumin significantly inhibited CYP1A1-mediated benzo(a)pyrene diol bioactivation in both oral SCC cells and intact oral mucosa [24].
• Curcumin activates the aryl hydrocarbon receptor yet significantly inhibits (-)-benzo(a)pyrene-7R-trans-7,8-dihydrodiol bioactivation in oral squamous cell carcinoma cells and oral mucosa [24].
• Taken together, these data provide evidence supporting a novel player (JNK), as well as its inhibitor (curcumin), in inflammation-mediated regulation of hepatobiliary transporters and correlate JNK-dependent RXR phosphorylation with reduced RXR-dependent hepatic gene expression [25].

Analytical, diagnostic and therapeutic context of curcumin

• Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound [26].
• Administration of pure or commercial grade curcumin in the diet to AOM-treated mice resulted in development of colon tumors which were generally smaller in number and size as compared to the control group of AOM-treated mice [27].
• Dietary curcumin also significantly suppressed the colon tumor volume by > 57% compared to the control diet [26].
• Taken together, our results show that PEITC and curcumin alone or in combination possess significant cancer-preventive activities in the PC-3 prostate tumor xenografts [12].
• An electrophoretic mobility shift assay revealed that activation of NF-kappaB induced by Taxol is down-regulated by curcumin [28].

References