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

Yan Jiao, John Wilkinson IV, Xiumin Di, Wei Wang, Heather Hatcher, Nancy D. Kock, Ralph D'Agostino Jr., Mary Ann Knovich, Frank M. Torti, and Suzy V. Torti*

Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC, United StatesDepartment of Pathology, Wake Forest University Health Sciences, Winston-Salem, NC, United StatesPublic Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, United StatesSection of Hematology/Oncology, Wake Forest University Health Sciences, Winston-Salem, NC, United StatesComprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, NC, United StatesDepartment of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC, United States
* Corresponding author; email: storti@wfubmc.edu

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 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 settling 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.