scholarly journals A new assay for intracellular measurement of inosine monophosphate dehydrogenase activity: a guide for better selection of patients for enzyme-targeted chemotherapy.

1994 ◽  
Vol 42 (1) ◽  
pp. 23-35 ◽  
Author(s):  
N Markovic ◽  
O Markovic ◽  
J Roberts ◽  
S Markovic
Keyword(s):  
Tumor Cell ◽  
Reference Values ◽  
Leukemia Cell ◽  
Human Tumor ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Drug Concentrations ◽  
Monophosphate Dehydrogenase

We developed a new cytochemical assay for identification of cells containing inosine monophosphate dehydrogenase (IMPDH) and measurement of tumor cell sensitivity to the escalating dose/schedule of the IMPDH pattern-targeting drugs. The assay is based on cytochemical principles for development of DH activity markers inside morphologically classified cells, image analysis for measuring the amount of this marker, and computer assistance for data management. The assay was optimized on a human leukemia cell line (K562-NS) and reference values for enzyme activity were established. Assay specificity was determined with different substrates and enzyme inhibitors. Sensitivity depends on the measuring instrument (image analyzing system), and the precision of the biological model used for assessment of reference values was high. IMPDH-positive malignant cells were found in all specimens obtained from acute leukemia and solid tumor patients (13/13 and 29/29) and in four human tumor cell lines (K562, K562-NS, HL60, and HL60-M). Cells of the K562-NS line were exposed to tiazofurin and ribavirin in conventional assays for assessment of drug-induced acute and subacute toxicity/sensitivity. A reduction of IMPDH activity was recorded at drug concentrations below the range at which cell damage appeared.

Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 996-1002 ◽  
Author(s):  
Marie-Véronique Clément ◽  
Jayshreekumari L. Hirpara ◽  
Sanaul-Haq Chawdhury ◽  
Shazib Pervaiz
Keyword(s):  
Cell Death ◽  
Natural Product ◽  
Tumor Cells ◽  
Leukemia Cell ◽  
Human Tumor ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Resveratrol Treatment ◽  
Dose Dependent Increase ◽  
Dose Dependent

Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity. © 1998 by The American Society of Hematology.

Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 996-1002 ◽  
Author(s):  
Marie-Véronique Clément ◽  
Jayshreekumari L. Hirpara ◽  
Sanaul-Haq Chawdhury ◽  
Shazib Pervaiz
Keyword(s):  
Cell Death ◽  
Natural Product ◽  
Tumor Cells ◽  
Leukemia Cell ◽  
Human Tumor ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Resveratrol Treatment ◽  
Dose Dependent Increase ◽  
Dose Dependent

Abstract Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity. © 1998 by The American Society of Hematology.

scholarly journals Human Inosine Monophosphate Dehydrogenase 2: Cryo-EM of Highly Flexible Filaments to Near Atomic Resolution

2018 ◽  
Vol 114 (3) ◽  
pp. 62a
Author(s):  
Matthew C. Johnson ◽  
Anika Burrell ◽  
Sajitha Anthony ◽  
Jeffrey Peterson ◽  
Justin Kollman
Keyword(s):  
Atomic Resolution ◽  
Inosine Monophosphate Dehydrogenase ◽  
Inosine Monophosphate ◽  
Monophosphate Dehydrogenase

scholarly journals In Vitro Combination of Amdoxovir and the Inosine Monophosphate Dehydrogenase Inhibitors Mycophenolic Acid and Ribavirin Demonstrates Potent Activity against Wild-Type and Drug-Resistant Variants of Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 48 (11) ◽  
pp. 4387-4394 ◽  
Author(s):  
Katyna Borroto-Esoda ◽  
Florence Myrick ◽  
Joy Feng ◽  
Jerry Jeffrey ◽  
Phillip Furman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Mycophenolic Acid ◽  
Inosine Monophosphate Dehydrogenase ◽  
Wild Type ◽  
Inosine Monophosphate ◽  
Immunodeficiency Virus ◽  
Monophosphate Dehydrogenase

ABSTRACT Amdoxovir [(−)-β-d-2,6-diaminopurine dioxolane (DAPD)] is a nucleoside analogue reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) replication. DAPD is deaminated by adenosine deaminase to the guanosine analogue dioxolane guanosine (DXG), which is subsequently phosphorylated to the corresponding 5′ triphosphate (DXG-TP). DXG-TP competes with the natural substrate dGTP for binding to the enzyme-nucleic acid complex. Mycophenolic acid (MPA) and ribavirin (RBV), inhibitors of inosine monophosphate dehydrogenase (IMPDH), inhibit the de novo synthesis of guanine nucleotides, including dGTP. Reducing the intracellular levels of dGTP would be expected to augment the antiviral activity of analogues of deoxyguanosine. In this study we examined the effect of MPA and RBV on the anti-HIV activity of DAPD and DXG. When tested against wild-type virus, both MPA and RBV decreased the 50% effective concentration (EC50) for DXG by at least 10-fold. In contrast, both MPA and RBV increase the EC50 value for zidovudine. MPA and RBV completely reversed the resistance to DXG observed with HIV isolates containing mutations which confer partial resistance to DAPD and DXG. Similarly, when tested against a mutant virus fully resistant to inhibition by DAPD (K65R/Q151M), MPA and RBV reduced the EC50 for DAPD to within twofold of that for the wild type. The combination of MPA or RBV with DAPD or DXG did not result in increased cytotoxicity or reduced levels of mitochondrial DNA when tested at physiologically relevant concentrations. These studies suggest a potential role for the use of IMPDH inhibitors in combination therapy with amdoxovir in the treatment of HIV.

scholarly journals 2-Chloro-2′-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4

Leukemia ◽  
2000 ◽  
Vol 14 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Y Nomura ◽  
O Inanami ◽  
K Takahashi ◽  
A Matsuda ◽  
M Kuwabara
Keyword(s):  
Cell Line ◽  
Fas Ligand ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Human Leukemia Cell ◽  
Human Leukemia Cell Line

Production of high levels of interleukin 1-like activity by the SPI-802 human leukemia cell line with E receptors

1984 ◽  
Vol 89 (1) ◽  
pp. 122-131 ◽  
Author(s):  
Atsushi Komiyama ◽  
Yukiaki Miyagawa ◽  
Kohki Aoyama ◽  
Taro Akabane ◽  
Yoshio Uehara
Keyword(s):  
Cell Line ◽  
Interleukin 1 ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Human Leukemia Cell ◽  
Human Leukemia Cell Line
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