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BioMed Research International
Volume 2015 (2015), Article ID 968981, 11 pages
Research Article

Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

1AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary
2Department of Pharmaceutical Technology, University of Szeged, Eötvös u 6, Szeged 6720, Hungary
3Department of Hematology, Institute of Internal Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen 4032, Hungary
4Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Temesvári Körút 62, Szeged 6726, Hungary

Received 26 February 2015; Accepted 4 March 2015

Academic Editor: Walter Jaeger

Copyright © 2015 L. I. Nagy et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.