Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator.
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.
Jiao
Yan
Y
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Wilkinson
John
J
Di
Xiumin
X
Wang
Wei
W
Hatcher
Heather
H
Kock
Nancy D
ND
D'Agostino
Ralph
R
Knovich
Mary Ann
MA
Torti
Frank M
FM
Torti
Suzy V
SV
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D003474:Curcumin / Q000009:adverse effects* / Q000494:pharmacology; D005526:Food, Formulated; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects* / Q000494:pharmacology; D019266:Iron, Dietary / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014168:Transferrin / Q000032:analysis / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D006454:Hemoglobins; D064451:Hepcidins; D007502:Iron Chelating Agents; D019266:Iron, Dietary; D014168:Transferrin; D003474:Curcumin