title: Curcumin and its analogue induce apoptosis in leukemia cells and have additive effects with bortezomib in cellular and xenograft models.
abstract: 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.
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: L I
authors.initials: LI
authors.lastname: Nagy
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: L Z
authors.initials: LZ
authors.lastname: Fehér
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: G J
authors.initials: GJ
authors.lastname: Szebeni
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Gyuris
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Eötvös u 6, Szeged 6720, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Sipos
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: R
authors.initials: R
authors.lastname: Alföldi
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Ózsvári
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Hackler
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Balázs
authors.affiliation: Department of Hematology, Institute of Internal Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen 4032, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Batár
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Kanizsai
authors.affiliation: AVIDIN Ltd., Alsókikötő Sor 11, Szeged, Hungary ; Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Temesvári Körút 62, Szeged 6726, Hungary.
authors.forename: L G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069286:Bortezomib / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D023041:Xenograft Model Antitumor Assays
chemical_list: D000069286:Bortezomib; D003474:Curcumin