Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cdelta-dependent mechanisms.

Abstract:

:As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. In the present study, we report that NSC606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (AML) cells NB4 and U937 and inhibits the proliferation without cell death in breakpoint cluster region-Abelson murine leukemia (bcr-abl) kinase-carrying leukemic K562 cells. For apoptosis induction or growth arrest, nanomolar concentrations of NSC606985 are sufficient. At such low concentrations, this agent also significantly inhibits the clonogenic activity of hematopoietic progenitors from patients with AML. For apoptosis induction, NSC606985 rapidly induces the proteolytic activation of protein kinase Cdelta (PKCdelta) with loss of mitochondrial transmembrane potential (DeltaPsim) and caspase-3 activation. Cotreatment with rottlerin, a PKCdelta-specific inhibitor, completely blocks NSC606985-induced mitochondrial DeltaPsim loss and caspase-3 activation, while the inhibition of caspase-3 by z-DEVD-fluoromethyl ketone (Z-DEVD-fmk) only partially attenuates PKCdelta activation and apoptosis. These data indicate that NSC606985-induced PKCdelta activation is an early event upstream to mitochondrial DeltaPsim loss and caspase-3 activation, while activated caspase-3 has an amplifying effect on PKCdelta proteolysis. In addition, NSC606985-induced apoptosis by PKCdelta also involves caspase-3-independent mechanisms. Taken together, our results suggest that NSC606985 is a potential agent for the treatment of AML.

journal_name

Blood

journal_title

Blood

authors

Song MG,Gao SM,Du KM,Xu M,Yu Y,Zhou YH,Wang Q,Chen Z,Zhu YS,Chen GQ

doi

10.1182/blood-2004-10-4011

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

3714-21

issue

9

eissn

0006-4971

issn

1528-0020

pii

2004-10-4011

journal_volume

105

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Cyclosporine v methotrexate for graft-v-host disease prevention in patients given marrow grafts for leukemia: long-term follow-up of three controlled trials.

    abstract::One hundred seventy-nine patients with acute nonlymphoblastic leukemia in first remission (n = 75), chronic myelocytic leukemia in chronic or accelerated phase (n = 48) or leukemia in advanced stage (n = 56) were given HLA-identical marrow grafts and randomized to receive methotrexate or cyclosporine for prevention of...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Storb R,Deeg HJ,Fisher L,Appelbaum F,Buckner CD,Bensinger W,Clift R,Doney K,Irle C,McGuffin R

    更新日期:1988-02-01 00:00:00

  • Experimental Pseudomonas pneumonia in leukopenic dogs: comparison of therapy with antibiotics and granulocyte transfusions.

    abstract::Pseudomonas aeruginosa pneumonia was produced in dogs with radiation-induced leukopenia to study the comparative efficacy of several different therapies. In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/d...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dale DC,Reynolds HY,Pennington JE,Elin RJ,Herzig GP

    更新日期:1976-05-01 00:00:00

  • HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells.

    abstract::Hypoxia-inducible factor-1α (HIF1α), a master transcriptional regulator of the cellular and systemic hypoxia response, is essential for the maintenance of self-renewal capacity of normal HSCs. It is still unknown whether HIF1α has a role in survival regulation of leukemia stem cells (LSCs) in chronic myeloid leukemia ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-10-387381

    authors: Zhang H,Li H,Xi HS,Li S

    更新日期:2012-03-15 00:00:00

  • p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32).

    abstract::The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Louie DC,Offit K,Jaslow R,Parsa NZ,Murty VV,Schluger A,Chaganti RS

    更新日期:1995-10-15 00:00:00

  • Analysis of the origin of marrow cells in bone marrow transplant recipients using a Y-chromosome-specific in situ hybridization assay.

    abstract::A Y-chromosome-specific in situ hybridization assay was used to assess the frequency with which host bone marrow cells are retained after marrow grafting. The majority of patients (74%) showed the presence of both host and donor marrow cells when assayed 14 days after transplant. By 84 days posttransplant only 4% of t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Durnam DM,Anders KR,Fisher L,O'Quigley J,Bryant EM,Thomas ED

    更新日期:1989-11-01 00:00:00

  • A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma.

    abstract::Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regenera...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:

    authors: Link H,Boogaerts MA,Carella AM,Ferrant A,Gadner H,Gorin NC,Harabacz I,Harousseau JL,Hervé P,Holldack J

    更新日期:1992-11-01 00:00:00

  • Control of cell cycle progression in human natural killer cells through redox regulation of expression and phosphorylation of retinoblastoma gene product protein.

    abstract::Using thiol deprivation, we have previously shown that the response of natural killer (NK) cells to interleukin-2 (IL-2) is subject to redox regulation downstream of IL-2 binding and internalization. We have now used the IL-2-dependent cell line, NK3.3 to study redox regulation of NK cells further, and found that NK3....

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Yamauchi A,Bloom ET

    更新日期:1997-06-01 00:00:00

  • Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.

    abstract::Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large vo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Moake JL,Turner NA,Stathopoulos NA,Nolasco L,Hellums JD

    更新日期:1988-05-01 00:00:00

  • Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency.

    abstract::Reduced levels of somatic hypermutation (SHM) have recently been described in IgG-switched immunoglobulin genes in a minority of patients with common variable immunodeficiency (CVID), demonstrating a disruption of the normal linkage between isotype switch and SHM. To see if, irrespective of isotype, there is a tendenc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-12-4359

    authors: Andersen P,Permin H,Andersen V,Schejbel L,Garred P,Svejgaard A,Barington T

    更新日期:2005-01-15 00:00:00

  • Human microRNA-27a* targets Prf1 and GzmB expression to regulate NK-cell cytotoxicity.

    abstract::Perforin (Prf1) and granzyme B (GzmB) are essential effector molecules for natural killer (NK)-cell cytotoxicity, but how Prf1 and GzmB expression is regulated during arming of NK cells is poorly defined. We show that human microRNA (miR)-27a* is a negative regulator of NK-cell cytotoxicity by silencing Prf1 and GzmB ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-347526

    authors: Kim TD,Lee SU,Yun S,Sun HN,Lee SH,Kim JW,Kim HM,Park SK,Lee CW,Yoon SR,Greenberg PD,Choi I

    更新日期:2011-11-17 00:00:00

  • KRASG12D expression in lung-resident myeloid cells promotes pulmonary LCH-like neoplasm sensitive to statin treatment.

    abstract::Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/extracellular signal-regulated kinase (ERK) signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulm...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-02-770149

    authors: Kamata T,Giblett S,Pritchard C

    更新日期:2017-07-27 00:00:00

  • Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study.

    abstract::Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cell...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Losada AP,Wessman M,Tiainen M,Hopman AH,Willard HF,Solé F,Caballín MR,Woessner S,Knuutila S

    更新日期:1991-08-01 00:00:00

  • A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction.

    abstract::Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal prolifera...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Takemoto S,Matsuoka M,Yamaguchi K,Takatsuki K

    更新日期:1994-11-01 00:00:00

  • Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

    abstract::The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-11-467191

    authors: Zhang G,Yang L,Kim GS,Ryan K,Lu S,O'Donnell RK,Spokes K,Shapiro N,Aird WC,Kluk MJ,Yano K,Sanchez T

    更新日期:2013-07-18 00:00:00

  • Leukemia inhibitory factor upregulates cytokine expression by a murine stromal cell line enabling the maintenance of highly enriched competitive repopulating stem cells.

    abstract::Attempts to maintain or expand primitive hematopoietic stem cells in vitro without the concomitant loss of their differentiative and proliferative potential in vivo have largely been unsuccessful. To investigate this problem, we compared the ability of three cloned bone marrow (BM) stromal cell lines to support the gr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Szilvassy SJ,Weller KP,Lin W,Sharma AK,Ho AS,Tsukamoto A,Hoffman R,Leiby KR,Gearing DP

    更新日期:1996-06-01 00:00:00

  • Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia.

    abstract::Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These pa...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1182/blood-2002-11-3419

    authors: Solary E,Drenou B,Campos L,de Crémoux P,Mugneret F,Moreau P,Lioure B,Falkenrodt A,Witz B,Bernard M,Hunault-Berger M,Delain M,Fernandes J,Mounier C,Guilhot F,Garnache F,Berthou C,Kara-Slimane F,Harousseau JL,Groupe O

    更新日期:2003-08-15 00:00:00

  • Whole-exome sequencing to identify genetic risk variants underlying inhibitor development in severe hemophilia A patients.

    abstract::The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly complication of FVIII replacement therapy that affects up to 30% of previously untreated patients with severe hemophilia A. The development of inhibitors is a multifactorial complication i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-12-685735

    authors: Gorski MM,Blighe K,Lotta LA,Pappalardo E,Garagiola I,Mancini I,Mancuso ME,Fasulo MR,Santagostino E,Peyvandi F

    更新日期:2016-06-09 00:00:00

  • Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma.

    abstract::Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) ...

    journal_title:Blood

    pub_type: 杂志文章,meta分析

    doi:10.1182/blood-2014-06-583369

    authors: Mir MA,Maurer MJ,Ziesmer SC,Slager SL,Habermann T,Macon WR,Link BK,Syrbu S,Witzig T,Friedberg JW,Press O,LeBlanc M,Cerhan JR,Novak A,Ansell SM

    更新日期:2015-02-05 00:00:00

  • GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome.

    abstract::Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-01-0013

    authors: Hitzler JK,Cheung J,Li Y,Scherer SW,Zipursky A

    更新日期:2003-06-01 00:00:00

  • A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease.

    abstract::Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells prolifera...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-324210

    authors: Bagnara D,Kaufman MS,Calissano C,Marsilio S,Patten PE,Simone R,Chum P,Yan XJ,Allen SL,Kolitz JE,Baskar S,Rader C,Mellstedt H,Rabbani H,Lee A,Gregersen PK,Rai KR,Chiorazzi N

    更新日期:2011-05-19 00:00:00

  • Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin.

    abstract::Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes m...

    journal_title:Blood

    pub_type: 杂志文章,随机对照试验

    doi:10.1182/blood-2005-05-1938

    authors: Warkentin TE,Cook RJ,Marder VJ,Sheppard JA,Moore JC,Eriksson BI,Greinacher A,Kelton JG

    更新日期:2005-12-01 00:00:00

  • Detection of factor VIII inhibitors with the partial thromboplastin time.

    abstract::Variations of the partial thromboplastin time (PTT) were tested to determine the best screening method for detection of inhibitors of factor VIII. Variables tested included the duration of preincubation of a mixture of patient plasma and factor VIII source (normal plasma), the ratio of the patient plasma to the normal...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lossing TS,Kasper CK,Feinstein DI

    更新日期:1977-05-01 00:00:00

  • T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets.

    abstract::Monocytes and T helper (T(H)) cells rapidly infiltrate inflamed tissues where monocytes differentiate into inflammatory dendritic cells (DCs) through undefined mechanisms. Our studies indicate that T(H) cells frequently interact with monocytes in inflamed skin and elicit the differentiation of specialized DC subsets c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-03-341065

    authors: Alonso MN,Wong MT,Zhang AL,Winer D,Suhoski MM,Tolentino LL,Gaitan J,Davidson MG,Kung TH,Galel DM,Nadeau KC,Kim J,Utz PJ,Söderström K,Engleman EG

    更新日期:2011-09-22 00:00:00

  • Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus.

    abstract::Four of 9 PAX transcription factor genes have been associated with chromosomal translocations in human tumors, although their oncogenic potential has not yet been demonstrated in transgenic mouse models. The B-lymphoidPAX5 gene participates in the generation of the t(9;14)(p13;q32) translocation in germinal center B c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-03-009670

    authors: Souabni A,Jochum W,Busslinger M

    更新日期:2007-01-01 00:00:00

  • Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia.

    abstract::The promyelocytic leukemia (PML) tumor suppressor of acute promyelocytic leukemia (APL) is essential for a number of proapoptotic and growth-suppressive pathways as well as for the activity of differentiating agents such as retinoic acid (RA). In human APL, the dose of PML is reduced to heterozygosity given that one a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-07-2200

    authors: Gurrieri C,Nafa K,Merghoub T,Bernardi R,Capodieci P,Biondi A,Nimer S,Douer D,Cordon-Cardo C,Gallagher R,Pandolfi PP

    更新日期:2004-03-15 00:00:00

  • Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes.

    abstract::T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wieser M,Bonifer R,Oster W,Lindemann A,Mertelsmann R,Herrmann F

    更新日期:1989-04-01 00:00:00

  • Clinical relevance of decreased free protein S levels: results from a retrospective family cohort study involving 1143 relatives.

    abstract::Conflicting data have been reported on the risk for venous thrombosis in subjects with low free protein S levels. We performed a post-hoc analysis in a single-center retrospective thrombophilic family cohort, to define the optimal free protein S level that can identify subjects at risk for venous thrombosis. Relatives...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood-2008-08-174128

    authors: Lijfering WM,Mulder R,ten Kate MK,Veeger NJ,Mulder AB,van der Meer J

    更新日期:2009-02-05 00:00:00

  • 14-3-3 proteins in platelet biology and glycoprotein Ib-IX signaling.

    abstract::Members of the 14-3-3 family of proteins function as adapters/modulators that recognize phosphoserine/phosphothreonine-based binding motifs in many intracellular proteins and play fundamental roles in signal transduction pathways of eukaryotic cells. In platelets, 14-3-3 plays a wide range of regulatory roles in phosp...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2017-09-742650

    authors: Chen Y,Ruggeri ZM,Du X

    更新日期:2018-05-31 00:00:00

  • Plasma cell myeloma--new biological insights and advances in therapy.

    abstract::Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so th...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:

    authors: Barlogie B,Epstein J,Selvanayagam P,Alexanian R

    更新日期:1989-03-01 00:00:00

  • SRF is required for neutrophil migration in response to inflammation.

    abstract::Serum response factor (SRF) is a ubiquitously expressed transcription factor and master regulator of the actin cytoskeleton. We have previously shown that SRF is essential for megakaryocyte maturation and platelet formation and function. Here we elucidate the role of SRF in neutrophils, the primary defense against inf...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-06-507582

    authors: Taylor A,Tang W,Bruscia EM,Zhang PX,Lin A,Gaines P,Wu D,Halene S

    更新日期:2014-05-08 00:00:00