by Jun Yuan, David B. Lovejoy, and Des R. Richardson

Slides:



Advertisements
Similar presentations
An anti-CD19 antibody inhibits the interaction between P-glycoprotein (P-gp) and CD19, causes P-gp to translocate out of lipid rafts, and chemosensitizes.
Advertisements

Δ-Tocotrienol treatment is more effective against hypoxic tumor cells than normoxic cells: potential implications for cancer therapy  Akira Shibata, Kiyotaka.
A Novel Cinnamide YLT26 Induces Breast Cancer Cells Apoptosis via ROS-Mitochondrial Apoptotic Pathway in Vitro and Inhibits.
Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in.
The Combined Effects of Hematoporphyrin Monomethyl Ether-SDT and Doxorubicin on the Proliferation of QBC939 Cell Lines  Lei Liang, Sheng Xie, Lin Jiang,
Vascular Endothelial Growth Factor (VEGF)-Mediated Angiogenesis Is Associated with Enhanced Endothelial Cell Survival and Induction of Bcl-2 Expression 
Saikosaponin-D Enhances Radiosensitivity of Hepatoma Cells under Hypoxic Conditions by Inhibiting Hypoxia-Inducible Factor-1α Cell Physiol Biochem 2014;33:37-51.
Figure 1. Herbacetin binds to AKT1/2 and suppresses each respective kinase activity. The effect of herbacetin on (A) PI3K/AKT and (B) MAPK signaling pathway.
Figure 1. Herbacetin binds to AKT1/2 and suppresses each respective kinase activity. The effect of herbacetin on (A) PI3K/AKT and (B) MAPK signaling pathway.
In Cardiomyocyte Hypoxia, Insulin-Like Growth Factor-I-Induced Antiapoptotic Signaling Requires Phosphatidylinositol-3-OH-Kinase-Dependent and Mitogen-Activated.
Novel vitamin D3 analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D3, that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of.
Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model by Dong Li, Hong Yang, Hong Nan,
Amanda M. Nelson, Kathryn L. Gilliland, Zhaoyuan Cong, Diane M
Vemurafenib Induces Senescence Features in Melanoma Cells
2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells
by Pascal Gelebart, Mona Anand, Hanan Armanious, Anthea C
T3 increased J7-TRα1 cell migration and proliferation both in vitro and in vivo. T3 increased J7-TRα1 cell migration and proliferation both in vitro and.
Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to.
Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas by Pankaj Gupta,
by Kumudha Balakrishnan, William G. Wierda, Michael J
Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and.
Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines by Xiao-Fang.
by Christina K. Ullrich, Jerome E. Groopman, and Ramesh K. Ganju
by Kirsteen H. Maclean, John L. Cleveland, and John B. Porter
Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo by Min.
Reticulocyte-secreted exosomes bind natural IgM antibodies: involvement of a ROS-activatable endosomal phospholipase iPLA2 by Lionel Blanc, Céline Barres,
Human NK cell development in NOD/SCID mice receiving grafts of cord blood CD34+ cells by Christian P. Kalberer, Uwe Siegler, and Aleksandra Wodnar-Filipowicz.
Volume 144, Issue 2, Pages (February 2013)
Pegylated arginase I: a potential therapeutic approach in T-ALL
Volume 129, Issue 3, Pages (September 2005)
Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells by Aleksandar Petlickovski,
Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms by Man-Gen.
Arctigenin inhibits prostate tumor cell growth in vitro and in vivo
Effects of Betulinic Acid Alone and in Combination with Irradiation in Human Melanoma Cells  Edgar Selzer, Emilio Pimentel, Volker Wacheck, Werner Schlegel,
The Zinc Ionophore PCI-5002 Radiosensitizes Non-small Cell Lung Cancer Cells by Enhancing Autophagic Cell Death  Kwang Woon Kim, PhD, Christina K. Speirs,
Inhibition of pathologic retinal neovascularization by α-defensins
Cathepsin-B-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism of T-cell depletion by Marie-Cécile Michallet, Frederic Saltel,
Apoptotic Vascular Endothelial Cells Become Procoagulant
Volume 72, Issue 4, Pages (August 2007)
John F. Öhd, Katarina Wikström, Anita Sjölander  Gastroenterology 
a b MCF-7 TR2 MCF-7 TR2 (Fold change) MTT Assay , (Fold change)
by Eleanor J. Molloy, Amanda J. O'Neill, Julie J
Volume 116, Issue 5, Pages (May 1999)
Regulation of Akt-dependent cell survival by Syk and Rac
Volume 136, Issue 4, Pages e3 (April 2009)
Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3 by Chiharu Kawamura, Masahiro Kizaki, Kenji Yamato, Hideo.
Protodynamic Intracellular Acidification by cis-Urocanic Acid Promotes Apoptosis of Melanoma Cells In Vitro and In Vivo  Jarmo K. Laihia, Janne P. Kallio,
AT-101, a Pan-Bcl-2 Inhibitor, Leads to Radiosensitization of Non-small Cell Lung Cancer  Luigi Moretti, MD, Bo Li, MD, Kwang Woon Kim, PhD, Heidi Chen,
NF-κB Inhibition through Proteasome Inhibition or IKKβ Blockade Increases the Susceptibility of Melanoma Cells to Cytostatic Treatment through Distinct.
Volume 22, Issue 3, Pages (March 2015)
Volume 67, Issue 1, Pages (January 2005)
Imetelstat, a telomerase inhibitor, is capable of depleting myelofibrosis stem and progenitor cells by Xiaoli Wang, Cing Siang Hu, Bruce Petersen, Jiajing.
Volume 73, Issue 5, Pages (March 2008)
Volume 122, Issue 2, Pages (February 2002)
Death Receptor-Independent Apoptosis in Malignant Melanoma Induced by the Small- Molecule Immune Response Modifier Imiquimod  Michael P. Schön, B. Gregor.
PARP Determines the Mode of Cell Death in Skin Fibroblasts, but not Keratinocytes, Exposed to Sulfur Mustard  Dana Anderson, Betty Benton, Zhao-Qi Wang,
Activation of Akt as a Mechanism for Tumor Immune Evasion
The pathological role of Bax in cisplatin nephrotoxicity
Thomas S. Griffith, Elizabeth L. Broghammer  Molecular Therapy 
Green Tea Polyphenol Epigallocatechin-3-Gallate Suppresses Collagen Production and Proliferation in Keloid Fibroblasts via Inhibition of the STAT3-Signaling.
Volume 18, Issue 3, Pages (March 2010)
Volume 3, Issue 5, Pages (May 2001)
Bcl-2 and bcl-xL Antisense Oligonucleotides Induce Apoptosis in Melanoma Cells of Different Clinical Stages  Robert A. Olie, Christoph Hafner, Renzo Küttel,
Differential effects of simvastatin on mesangial cells
by Xuefang Cao, Xingming Deng, and W. Stratford May
Yoshinori Aragane, Akira Maeda, Chang-Yi Cui, Tadashi Tezuka 
N-3 PUFAs promote endometrial cancer cell apoptosis in vitro and in vivo. n-3 PUFAs promote endometrial cancer cell apoptosis in vitro and in vivo. HEC-1-A.
WP1066 induces caspase-dependent apoptosis.
Effect of BCAA on the progression of cell cycle, expression of p21CIP1, and induction of apoptosis in HepG2 cells in the presence and absence of visfatin.
Effect of SFN on the total activity and protein expression of HDACs in JB6 P+ cells. Effect of SFN on the total activity and protein expression of HDACs.
Presentation transcript:

by Jun Yuan, David B. Lovejoy, and Des R. Richardson Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment by Jun Yuan, David B. Lovejoy, and Des R. Richardson Blood Volume 104(5):1450-1458 September 1, 2004 ©2004 by American Society of Hematology

Structural formulas of the Fe chelators described in this study. Structural formulas of the Fe chelators described in this study. (A) General structure of the DpT analogs showing the numbering scheme used. (B) Structures of DFO, 311, 3-AP, and PKIH. (C) Structures of DpT, Dp2mT, Dp4mT, Dp44mT, Dp4eT, Dp4aT, and Dp4pT. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

The most effective DpT analogs and 311 (internal control) show selective antiproliferative activity against immortal SK-N-MC neuroepithelioma cells (S) compared with mortal MRC-5 fibroblasts (F). The most effective DpT analogs and 311 (internal control) show selective antiproliferative activity against immortal SK-N-MC neuroepithelioma cells (S) compared with mortal MRC-5 fibroblasts (F). Cells were incubated in the presence or absence of the chelators (0-25 μM) for 72 hours at 37° C.23 After this incubation period, cellular density was measured using the MTT assay. Cellular proliferation was expressed as a percentage of that found for the untreated cells. Each data point represents the mean of 2 replicates in a typical experiment of at least 3 to 5 experiments. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

Effect of the DpT analogs compared with DFO and 311 on 59Fe mobilization and cellular 59Fe uptake from 59Fe-Tf in SK-N-MC neuroepithelioma and M109 cells. Effect of the DpT analogs compared with DFO and 311 on 59Fe mobilization and cellular 59Fe uptake from 59Fe-Tf in SK-N-MC neuroepithelioma and M109 cells. (A) Effect of chelators on 59Fe mobilization from prelabeled SK-N-MC neuroepithelioma cells. Cells were prelabeled with 59Fe-Tf (0.75 μM) for 3 hours at 37° C, washed, and then reincubated for 3 hours at 37° C in the presence of medium alone (control) or medium containing the chelators (25 μM). (B) Effect of the chelators at preventing 59Fe uptake from 59Fe-Tf by SK-N-MC cells. Cells were incubated for 3 hours at 37° C in media containing either 59Fe-Tf (0.75 μM) alone (control) or 59Fe-Tf (0.75 μM) and the chelators (25 μM). After this incubation, the cells were washed and incubated with pronase (1 mg/mL) for 30 minutes at 4° C to measure internalized 59Fe.13,14 (C) Effect of the chelators on 59Fe mobilization from prelabeled M109 cells as a function of chelator concentration. M109 cells were prelabeled as described for panel A, then reincubated with the chelator (0.2-25 μM) for 3 hours at 37° C. (D) Effect of the chelators at preventing 59Fe uptake from 59Fe-Tf by M109 cells as a function of chelator concentration. M109 cells were incubated with 59Fe-Tf (0.75 μM) in the presence of the chelators (0.2-25 μM) for 3 hours at 37° C. Cells were washed and incubated with pronase as described for panel B. Results are expressed as the mean ± SD of 3 replicates in a typical experiment of 3 performed. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

Dose-dependent inhibition of M109 lung carcinoma growth in mice by Dp44mT and 3-AP. Dose-dependent inhibition of M109 lung carcinoma growth in mice by Dp44mT and 3-AP. (A) Dp44mT and, to a greater extent, 3-AP markedly decreased the growth of M109 lung carcinoma in mice after a 5-day treatment regimen. (B) Induction of apoptosis in tumors after injection of (i) vehicle control or (ii) Dp44mT, as determined using TUNEL assay. (A) 1 × 105 M109 cells were subcutaneously implanted in CD2F1 mice. The chelators Dp44mT and 3-AP were injected intravenously twice daily for 5 consecutive days starting on the fourth day after tumor implantation. Tumor weight was measured on the 12th day after implantation. n = 8 in each experimental group. Data were analyzed using the Student t test. *P < .05 compared with control. **P < .01 compared with control. ***P < .0001. (B) M109 lung carcinoma specimens from mice treated as for panel A with (i) vehicle control or (ii) Dp44mT were fixed in 10% (vol/vol) buffered formalin and embedded in paraffin. Sections were stained for apoptotic cells in situ using the TUNEL assay. Positive nuclei stained brown, and negative nuclei stained blue. Results in panel A are mean ± SEM for 3 experiments, whereas data in panel B are typical of results found in 3 separate experiments. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

Effect of Dp44mT on M109 cellular apoptosis or necrosis/late-stage apoptosis. Effect of Dp44mT on M109 cellular apoptosis or necrosis/late-stage apoptosis. (A) Chelator concentration. M109 cells were incubated with Dp44mT at 0 to 250 μM for 24 hours at 37° C. Cellular apoptosis and necrosis/late-stage apoptosis were measured using Annexin V–FITC and PI staining, respectively (see “Materials and methods”). (B) Incubation time. M109 cells were treated with Dp44mT (1 μM) for various incubation times (0-48 hours). Cellular apoptosis and necrosis/late-stage apoptosis were measured as described for panel A. Data plotted are mean ± SEM of 3 separate experiments. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

Effect of Dp44mT (1 μM) on the protein levels of active caspase-3, -8, and -9 and the activity of caspase-3, -8, and -9 in cultured M109 cells in the absence and presence of cell-permeable caspase inhibitors. Effect of Dp44mT (1 μM) on the protein levels of active caspase-3, -8, and -9 and the activity of caspase-3, -8, and -9 in cultured M109 cells in the absence and presence of cell-permeable caspase inhibitors. (A) Caspase-3, -8, and -9 levels after Dp44mT treatment at the indicated times as detected by Western blotting (top blots). Anti–β-actin antibody was used to ensure equal protein loading (bottom blot). (B) Densitometric analysis of the expression of caspase-3, -8, and -9 as a function of time normalized to β-actin. (C) Caspase activity induced by Dp44mT (1 μM) at 0 to 48 hours was expressed as a percentage of the 0-hour time value. (D) Cell-permeable inhibitors of caspase-3, -8, or -9 at 1 μM prevented activation of these enzymes when incubated with Dp44mT (1 μM) for 48 hours. Results are mean ± SEM of 3 separate experiments. Horizontal dashed line indicates 100%. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology

Effect of Dp44mT (1 μM) in cultured M109 cells on the holocytochrome c (h-cytc) levels in cytosolic and stromal-mitochondrial membrane (SMM) fractions and mitochondrial protein levels of Bcl-2 and Bax. Effect of Dp44mT (1 μM) in cultured M109 cells on the holocytochrome c (h-cytc) levels in cytosolic and stromal-mitochondrial membrane (SMM) fractions and mitochondrial protein levels of Bcl-2 and Bax. (A) Cytosolic and SMM fractions of M109 cells were separated and subjected to Western blotting with anti–h-cytc antibody. The blot was reprobed with an anti–β-actin antibody to ensure equal protein loading. Densitometric analyses are shown beneath the blots; expression is normalized to β-actin. (B) Protein levels of Bcl-2 and Bax were determined through Western blotting using the SMM fraction of M109 cells after incubation with Dp44mT for 0 to 48 hours. Anti–β-actin antibody was used to ensure equal protein loading. Densitometric analysis is shown beneath each blot, where expression is normalized to β-actin. Results in panels A and B are representative of 3 experiments. Jun Yuan et al. Blood 2004;104:1450-1458 ©2004 by American Society of Hematology