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.

MMRC announces Phase 1B Study of Elotuzumab (HuLuc63) Monoclonal Antibody in combination with REVLIMID and dexamethasone

The Multiple Myeloma Research Consortium (MMRC) today announced the initiation of a three-drug combination study of elotuzumab (also known as HuLuc63), a humanized anti-CS1 monoclonal IgG1 antibody administered intravenously, in combination with REVLIMID(R) (lenalidomide), and dexamethasone for the treatment of multiple myeloma in patients who are experiencing a relapse.

Emory University's Winship Cancer Institute, Washington University, and St. Vincent's Comprehensive Cancer Center of Saint Vincent Catholic Medical Centers of New York will evaluate the maximum tolerated dose of elotuzumab in combination with label dosing of lenalidomide and dexamethasone. The multi-center, open-label, dose-escalation Phase Ib study will enroll up to 26 patients.

"This three drug combination study is a pivotal study for patients with relapsed multiple myeloma as they may benefit from the synergistic effects of a new monoclonal antibody with two currently available drugs", said Principal Investigator, Sagar Lonial, MD, Associate Professor of Medicine, at Emory University's Winship Cancer Institute. "We look forward to testing this promising new combination."

About Elotuzumab
Elotuzumab (or HuLuc63) is a humanized monoclonal antibody under development by PDL BioPharma that binds to human CS1, a cell-surface glycoprotein that is highly and universally expressed on multiple myeloma cells but minimally expressed on normal cells. The antibody is currently being evaluated in Phase I clinical studies as a monotherapy and combination therapy for the treatment of relapsed multiple myeloma.

REVLIMID approved in Canada

Celgene announced that its oral cancer drug REVLIMID (lenalidomide) has received marketing authorization approval from Health Canada for use in combination with dexamethasone as a treatment for patients with multiple myeloma who have received at least one prior therapy. Multiple myeloma is the second most commonly diagnosed blood cancer worldwide.

Approximately 6,000 Canadians have the disease and another 2,000 are diagnosed each year.

The authorization from Health Canada was based upon the safety and efficacy results of two large, randomized pivotal Phase III special protocol assessment trials, North American Trial MM-009 and International Trial MM-010 evaluating REVLIMID plus dexamethasone in multiple myeloma patients who have received at least one prior therapy--both published in the New England Journal of Medicine in November 2007.

REVLIMID is currently approved in the United States, the European Union, Argentina and Switzerland in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy and in Australia in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy. REVLIMID is also approved in Canada, the United States and Argentina for transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. REVLIMID has obtained Orphan Drug designation in the EU, U.S., Switzerland and Australia.