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.

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

“…In AML cells, curcumin induces apoptosis and has additive effects with bortezomib and arsenic trioxide (Nagy et al, ; Sanchez et al, ; Sharma et al, ). The coformulation of curcumin and doxorubicin in poly(D, L‐lactide‐co‐glycolide) nanoparticles inhibited the development of drug resistance by inhibiting the mRNA expressions of MDR1 and B‐cell lymphoma 2 ( BCL2 ) in K562 cells and thus prolonged the effect of doxorubicin (Misra & Sahoo, ).…”

“…Curcumin can inhibit the cells of several cancers, including leukemia, colon carcinoma, breast cancer, pancreatic carcinoma, and lung cancer (Benzel & Fendrich, ; Mantzorou, Pavlidou, Vasios, Tsagalioti, & Giaginis, ; Martinez‐Castillo et al, ; Panda, Chakraborty, Sarkar, Khan, & Sa, ; Soleimani, Sahebkar, & Hosseinzadeh, ). Curcumin and its analogs have potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60 (Nagy et al, ; Sanchez, Simon, Calvino, de Blas, & Aller, ; Shakor et al, ). In several phase I clinical trials, the biological effects of curcumin have been noted in patients with malignancies, including pancreatic cancer, multiple myeloma, and advanced colorectal cancer, refractory to standard chemotherapy.…”

Curcumin induces apoptosis in human leukemic cell lines through an IFIT2-dependent pathway

“…5,6 Several studies indicated that curcumin can suppress the proliferation of leukemia and induce cell death. [7][8][9] Besides, it shows no significant side effects compared with other chemotherapeutic drugs. 10 Therefore, curcumin may represent a new therapeutic strategy for treatment of leukemia.…”

“…11 Considerable work has been conducted to explore how curcumin works. [7][8][9] Extensive research over the last decades has revealed that curcumin exerts anticancer effect through affecting numerous molecular and biochemical cascades.…”

Optimized synthesis routes and biological application of n-peptide-6-amino-D-luciferin conjugates

“…Alexa Fluor R 488 was bought from Thermo Fisher Scientific (Waltham, MA, USA). N-Z-DEVD-aLuc, C150 (Nagy et al, 2015;Hackler et al, 2016), and Ac-915 (Nagy et al, 2013) were synthesized by Avidin Ltd., (Szeged, Hungary). Thin layer chromatography was performed on silica gel plates 60 F 254 from Merck (Darmstadt, Germany).…”