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

被引:198
|
作者
Jiao, Yan [2 ]
Wilkinson, John [2 ,3 ]
Di, Xiumin [2 ]
Wang, Wei [2 ]
Hatcher, Heather [2 ]
Kock, Nancy D. [4 ]
D'Agostino, Ralph, Jr. [3 ,5 ]
Knovich, Mary Ann [6 ]
Torti, Frank M. [2 ,3 ]
Torti, Suzy V. [1 ,3 ]
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA
[3] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA
[4] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA
[5] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA
[6] Wake Forest Univ, Bowman Gray Sch Med, Hematol Oncol Sect, Winston Salem, NC 27157 USA
基金
美国国家卫生研究院;
关键词
KAPPA-B ACTIVATION; DIETARY CURCUMIN; DETOXIFICATION ENZYMES; REGULATORY PROTEINS; GENE-EXPRESSION; MICE; INHIBITION; HEPCIDIN; LIVER; RAT;
D O I
10.1182/blood-2008-05-155952
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease. ( Blood. 2009; 113: 462-469)
引用
收藏
页码:462 / 469
页数:8
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