The Combination of Flavokawain B and Daunorubicin Induces Apoptosis in Human Myeloid Leukemic Cells by Modifying NF-κB.

BACKGROUND/AIM Flavokawain B (FKB), is a natural chalcone isolated from kava root that induces apoptosis in cancer cells. Herein we investigated the effects of combination of FKB and daunorubicin (DNR) on human leukemic cells. MATERIALS AND METHODS Cell viability and death were assessed by the MTS assay and flow cytometry. NK-κB was detected by western blotting. RESULTS FKB alone and in combination with DNR reduced the viable cell numbers of four leukemic cell lines. FKB itself induced apoptosis of an acute myeloid cell line, HL-60. Because the additive effect of DNR and FKB was most obvious in HL-60 cells, subsequent experiments were performed with HL-60 cells. Combined treatment of the two compounds increased NF-κB activation at 12 h. CONCLUSION A combination treatment of DNR and FKB may improve the anticancer effects of DNR in DNR-resistant acute myeloid leukemia.

[1]  B. Comrie,et al.  Stems , 2020, A Grammar of Akabea.

[2]  Xiaoli Zhang,et al.  Discovery of Anticancer Agents of Diverse Natural Origin. , 2016, Anticancer research.

[3]  M. E. Shaker,et al.  The SMAC mimetic BV6 induces cell death and sensitizes different cell lines to TNF-α and TRAIL-induced apoptosis , 2016, Experimental biology and medicine.

[4]  Chang Seong Kim,et al.  Nicotine-Induced Apoptosis in Human Renal Proximal Tubular Epithelial Cells , 2016, PloS one.

[5]  A. Mes-Masson,et al.  The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin , 2016, Scientific Reports.

[6]  L. Zitvogel,et al.  STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells. , 2015, Cancer research.

[7]  T. Aas,et al.  Concomitant inactivation of the p53‐ and pRB‐ functional pathways predicts resistance to DNA damaging drugs in breast cancer in vivo , 2015, Molecular oncology.

[8]  Jinlin Lin,et al.  P53 deficiency-induced Smad1 upregulation suppresses tumorigenesis and causes chemoresistance in colorectal cancers. , 2015, Journal of molecular cell biology.

[9]  Xue-Qun Luo,et al.  Flavokawain B inhibits the growth of acute lymphoblastic leukemia cells via p53 and caspase-dependent mechanisms , 2015, Leukemia & lymphoma.

[10]  J. Cortes,et al.  New treatment for acute myelogenous leukemia , 2015, Expert opinion on pharmacotherapy.

[11]  P. Lønning,et al.  DNA Methylation Status of Key Cell-Cycle Regulators Such as CDKNA2/p16 and CCNA1 Correlates with Treatment Response to Doxorubicin and 5-Fluorouracil in Locally Advanced Breast Tumors , 2014, Clinical Cancer Research.

[12]  A. Omar,et al.  Flavokawain A Induces Apoptosis in MCF-7 and MDA-MB231 and Inhibits the Metastatic Process In Vitro , 2014, PloS one.

[13]  Jiwang Zhang,et al.  Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML , 2014, The Journal of experimental medicine.

[14]  M. Levis,et al.  The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond , 2014, Therapeutic advances in hematology.

[15]  K. Bradstock,et al.  Antibody therapy for acute myeloid leukaemia , 2014, British journal of haematology.

[16]  O. Abdel-Wahab,et al.  Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. , 2013, Blood.

[17]  Tony Kouzarides,et al.  Targeting epigenetic readers in cancer. , 2012, The New England journal of medicine.

[18]  X. Zi,et al.  Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line , 2012, The journal of obstetrics and gynaecology research.

[19]  P. Lønning,et al.  Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer , 2012, Breast Cancer Research.

[20]  Jie Sun,et al.  Autophagy Inhibition Enhances Daunorubicin-Induced Apoptosis in K562 Cells , 2011, PloS one.

[21]  P. Chueh,et al.  Flavokawain B, a novel chalcone from Alpinia pricei Hayata with potent apoptotic activity: Involvement of ROS and GADD153 upstream of mitochondria-dependent apoptosis in HCT116 cells. , 2010, Free radical biology & medicine.

[22]  J. Olson,et al.  Comparative Genome-Wide Screening Identifies a Conserved Doxorubicin Repair Network That Is Diploid Specific in Saccharomyces cerevisiae , 2009, PloS one.

[23]  I. Weissman,et al.  Stems Cells and the Pathways to Aging and Cancer , 2008, Cell.

[24]  Michael Karin,et al.  NF-kappaB and cancer-identifying targets and mechanisms. , 2008, Current opinion in genetics & development.

[25]  E. Estey,et al.  Acute myeloid leukemia and myelodysplastic syndromes in older patients. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  H. Gundacker,et al.  Age and acute myeloid leukemia. , 2006, Blood.

[27]  X. Zi,et al.  Flavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells by involvement of Bax protein-dependent and mitochondria-dependent apoptotic pathway and suppresses tumor growth in mice. , 2005, Cancer research.

[28]  Agnes B. Kane,et al.  Central Role of the Threonine Residue within the p+1 Loop of Receptor Tyrosine Kinase in STAT3 Constitutive Phosphorylation in Metastatic Cancer Cells , 2004, Molecular and Cellular Biology.

[29]  J. Cheong,et al.  Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable , 2003, Leukemia.

[30]  G. Laurent,et al.  Protein kinase Czeta mediated Raf-1/extracellular-regulated kinase activation by daunorubicin. , 2003, Blood.

[31]  J. Jaffrezou,et al.  Signaling pathways activated by daunorubicin. , 2001, Blood.

[32]  J. Darnell,et al.  The role of STATs in transcriptional control and their impact on cellular function , 2000, Oncogene.

[33]  D. Marquardt,et al.  Mechanisms of multidrug resistance in HL60 cells: detection of resistance-associated proteins with antibodies against synthetic peptides that correspond to the deduced sequence of P-glycoprotein. , 1990, Cancer research.

[34]  J. Tamburini,et al.  Single cell analysis of phosphoinositide 3-kinase/Akt and ERK activation in acute myeloid leukemia by flow cytometry. , 2006, Haematologica.

[35]  H. J. Kim,et al.  NF-kappaB and IKK as therapeutic targets in cancer. , 2006, Cell death and differentiation.

[36]  M. Weber,et al.  Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts. , 2002, Leukemia.

[37]  B. Ness,et al.  The bone marrow stromal microenvironment influences myeloma therapeutic response in vitro , 2001, Leukemia.