Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator

Jiao, Yan; Wilkinson, John; Di, Xiumin; Wang, Wei; Hatcher, Heather; Kock, Nancy D.; D’Agostino, Ralph B.; Knovich, Mary Ann; Torti, Frank M.; Torti, Suzy V.

doi:10.1182/blood-2008-05-155952

Cited by 231 publications

(191 citation statements)

References 52 publications

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“…Curcumin was recently found to be an active iron chelator in vivo and to induce a state of overt iron deficiency anemia in mice fed with diets poor in iron. 58 This suggests that curcumin has the potential to affect systemic iron metabolism, particularly in people with suboptimal iron status. 58,59 Curcumin has also been shown to inhibit the activity of the drug-metabolizing enzymes cytochrome P450, glutathione-S-transferase, and UDP-glucuronosyltransferase.…”

Section: Dear Editormentioning

confidence: 99%

“…58 This suggests that curcumin has the potential to affect systemic iron metabolism, particularly in people with suboptimal iron status. 58,59 Curcumin has also been shown to inhibit the activity of the drug-metabolizing enzymes cytochrome P450, glutathione-S-transferase, and UDP-glucuronosyltransferase. 8,[60][61][62] The inhibition of these enzymes in people taking curcumin may lead to an undesired increase in the plasma concentrations of some drugs and cause toxicity.…”

Section: Dear Editormentioning

confidence: 99%

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The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

304

210

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Dear Editor,Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa. The powdered rhizome of this plant, called turmeric, is a common ingredient in curry powders and has a long history of use in traditional Asian medicine for a wide variety of disorders. In the last decade a large number of reports have been published on the beneficial effects of curcumin, and it has repeatedly been claimed that this natural product is efficient and safe for the prevention and treatment of several diseases including cancer. 1-3 It is not surprising, therefore, that curcumin is currently sold as a dietary supplement and that numerous clinical trials are ongoing or recruiting participants to evaluate curcumin activity. But there is accumulating evidence that curcumin may not be so effective and safe. Because such evidence is not generally acknowledged, the purpose of this letter is to briefly review the negative properties of curcumin so that they can be balanced against its beneficial effects.Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies in which curcumin was tested at concentrations in the micromolar range. Several reports have demonstrated, however, that the plasma concentrations of curcumin in people taking relatively high oral doses of this compound are very low, typically in the nanomolar range (reviewed in Ref. 4). For instance, a recent study examined the pharmacokinetics of a curcumin preparation in 12 healthy human volunteers 0.25-72 hr after an oral dose of 10 or 12 g. Using a high-performance liquid chromatography assay with a limit of detection of 50 ng mL À1 , only 1 subject had detectable free curcumin at any of the time points assayed. 5 The fact that curcumin also undergoes extensive metabolism in intestine and liver 6,7 means that high concentrations of curcumin cannot be achieved and maintained in plasma and tissues after oral ingestion. This is a major obstacle for the clinical development of this agent and suggests that the therapeutic potential of oral curcumin is limited. The low clinical efficiency of curcumin in the treatment of several chronic diseases such as Alzheimer's disease and cardiovascular diseases has been discussed recently. 8 As far as cancer is concerned, in vitro studies have demonstrated that cancer cells do not die unless they are exposed to curcumin concentrations of 5-50 lM for several hours. 4,9,10 Because of its poor bioavailability, these concentrations are not achieved outside the gastrointestinal tract when curcumin is taken orally. Because of its extensive metabolism in intestine and liver, these concentrations cannot be maintained for several hours in the gastrointestinal tract. This suggests that the chemotherapeutic potential of oral curcumin is limited even for the treatment of cancers of the gastrointestinal tract. Accordingly, when 15 patients with advanced colorectal cancer were treated with curcumin at daily doses of 3.6 g for up to 4 months, no partial responses to treatment or decreases in tu...

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Section: Dear Editormentioning

confidence: 99%

Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

304

210

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“…Curcumin has been shown to act as a cancer chemopreventive and chemotherapeutic agent (Chuang, 2000;Goel et al, 2008;Hatcher et al, 2008;Jiao et al, 2008). Curcumin, a polyphenolic compound, has been successfully used for treatment of various diseases such as allergies, arthritis, diabetes, Alzheimer's disease and other chronic diseases Manolova et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis

Kar¹,

Biswas²,

Banerjee³

2016

Biomed Res Ther

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Abstract-Introduction: Pulmonary Fibrosis can severely disrupt lung function. The cause of Idiopathic Pulmonary Fibrosis (IPF) is still unclear. The treatment currently available for IPF provides minimal benefits. Bleomycin is used in research to induce experimental pulmonary fibrosis in animals. Plant flavonoids such as fisetin and curcumin are known for their anti-inflammatory properties. The aim was to demonstrate the path of physiological changes in bleomycin induced IPF and to further evaluate the reversal and ameliorative potentials of some plant flavonoids and their nanocomposites. Bleomycin administration is known to damage the lung epithelial cells resulting in lower cell numbers. Methods: The Balb/c mice were used as models for bleo-induced IPF. Inflammation was measured by the generation of ROS, RONI, and histological assessment. Cell proliferation was measured by MTS assay and CFU assay. Results: Our colony-forming assay in BALF also demonstrated a reduction (1.65 fold) in colony-forming unit after bleomycin administration. The number of colonies increased upon treatment with fisetin(1.20 fold) and curcumin (1.13 fold) respectively. MTT proliferation assay demonstrated a significant increase in the number of viable cells upon treatment with curcumin (1.42 fold) and fisetin (1.74 fold) respectively, in the lung. The NBT assay demonstrated a significant effect of curcumin in BALF, lung and peripheral blood. A significant effect of fisetin was observed in BALF and peripheral blood. Conclusion: These findings were also supported by the histological analyses of the lung samples. Curcumin showed highest potential for the treatment of IPF and fisetin showed its ameliorative effect.

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“…Based on the encouraging preclinical and phase I clinical data, several additional human trials have been initiated and are currently enrolling patients. This includes trials testing the activity of curcumin in patients with colon cancer, pancreatic cancer, multiple myeloma, and myelodisplasia (Jiao et al, 2009). Nanoparticles have promising applications in medicine (Jiao et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…It can suppress TNF expression induced by numerous stimuli and in numerous cell types. Recent work has suggested that curcumin acts as a cancer chemopreventive and chemotherapeutic agent (Chuang et al, 2000;Goel et al, 2008;Hatcher et al, 2008;Jiao et al, 2009). Curcumin inhibits activation of nuclear factor κB through blockade of IκB kinase, and inhibits activation of cyclooxygenase 2 (COX2).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic use of fisetin, curcumin, and mesoporous carbon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis

Kar¹,

Konsam²,

Hore³

et al. 2015

Biomed Res Ther

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Abstract-Idiopathic pulmonary fibrosis (IPF) is a devastating disease of unknown etiology, for which there is no curative pharmacological therapy. Bleomycin, an anti-neoplastic agent that causes lung fibrosis in human patients has been used extensively in rodent models to mimic IPF. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients responds to such a therapy. IPF is a progressive, ultimately fatal disorder for which substantive medical therapy is desperately needed. Fisetin is a flavonol which inhibits the activity of several pro-inflammatory cytokines. The polyphenol curcumin is used to treat inflammatory diseases, abdominal disorders, and a variety of other ailments. The aim of this study was to evaluate the beneficial effect of fistine, curcumin and mesoporous carbaon nanoparticle (MCN) loaded fisetin as an anti-inflammatory agents against bleomycin-induced changes in mice with IPF. In our study, flavonoids showed their anti fibrotic action. The inflammatory cell count was greatly increased for bleo treated individuals and effectiveness of fisein was increased after addition of MCN particles with it, curcumin also showed anti-inflammatory effects. In another experiment, bleomycin effectively inhibits the cellular recruitment to the spleen and treatment with fisetin, and curcumin increases the cellular recruitment in spleen. Colony count was also increased in MCN+fisetin treated groups, and it was statistically significant. We also observed the increased level of cytokines with fisetin treatment, with curcumin treatment and with MCN +fisetin treatment as compared to the bleo treated sample. In conclusion, the present research suggests that fisetin and curcumin and MCN loaded fisetin may be a promising therapeutic agent for bleomycin-induced changes in mice with IPF. This will open up new perspectives for a potential role of these drugs as a molecular target in Idiopathic pulmonary fibrosis.

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Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator

Cited by 231 publications

References 52 publications

The dark side of curcumin

The dark side of curcumin

Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis

Therapeutic use of fisetin, curcumin, and mesoporous carbon nanoparticle loaded fisetin in bleomycin-induced idiopathic pulmonary fibrosis

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