Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells.

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Abstract Text:

Elizabeth P Ryan,Timothy P Bushnell,Alan E Friedman,Irfan Rahman,Richard P Phipps,Elizabeth P Ryan,Timothy P Bushnell,Alan E Friedman,Irfan Rahman,Richard P Phipps,

We recently reported that inhibition of Cyclooxygenase-2 (Cox-2) reduced human B-CLL proliferation and survival. Herein, we investigated the mechanisms whereby small molecule Cox-2 selective inhibitors, SC-58125 (a Celebrex analog) and CAY10404 blunt survival of human B-cell lymphomas and chronic lymphocytic leukemia B-cells. SC-58125 and OSU03012 (a Celebrex analog that lacks Cox-2 inhibitory activity) both decreased intracellular glutathione (GSH) content in malignant human B-cells, as well as in Cox-2 deficient mouse B-cells. This new finding supports Cox-2 independent effects of SC-58125. Interestingly, SC-58125 also significantly increased B-cell reactive oxygen species (ROS) production, suggesting that ROS are a pathway that reduces malignant cell survival. Addition of GSH ethyl ester protected B lymphomas from the increased mitochondrial membrane permeability and reduced survival induced by SC-58125. Moreover, the SC-58125-mediated GSH depletion resulted in elevated steady-state levels of the glutamate cysteine ligase catalytic subunit mRNA and protein. These new findings of increased ROS and diminished GSH levels following SC-58125 exposure support novel mechanisms whereby a Cox-2 selective inhibitor reduces malignant B-cell survival. These observations also support the concept that certain Cox-2 selective inhibitors may have therapeutic value in combination with other drugs to kill malignant B lineage cells.

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Publishing Authors By Initials

EP Ryan,TP Bushnell,AE Friedman,I Rahman,RP Phipps,EP Ryan,TP Bushnell,AE Friedman,I Rahman,RP Phipps,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer immunology, immunotherapy : CII

VOLUME: 57

Page Numbers: 347-58

Journal Abbreviation: Cancer Immunol. Immunother.

ISSN: 0340-7004

DAY: 1

MONTH: 08

YEAR: 2007

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8605732

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells.

AFFILIATION: Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA, Richard_Phipps@urmc.rochester.edu.

Country: Germany

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Cancer Immunol Immunother

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells Related Publications

• Accessing Care: Use of a Specialized Women's Emergency Care Facility for Nonemergent Problems.
• Activated human T lymphocytes express cyclooxygenase-2 and produce proadipogenic prostaglandins that drive human orbital fibroblast differentiation to adipocytes.
• Adaptive style and differences in parent and child report of health-related quality of life in children with cancer.
• Adaptive style in children with cancer: implications for a positive psychology approach.
• Chronic poverty and childhood asthma in the Maritimes versus the rest of Canada.
• Consequences of inadequate sex education in the United States.
• CpG oligodeoxynucleotides induce cyclooxygenase-2 in human B lymphocytes: implications for adjuvant activity and antibody production.
• Cyclooxygenase-2 independent effects of cyclooxygenase-2 inhibitors on oxidative stress and intracellular glutathione content in normal and malignant human B-cells.
• Cyclooxygenase-2 inhibition attenuates antibody responses against human papillomavirus-like particles.
• Effect of soy protein on testosterone levels.
• Effective and organ doses from thoron decay products at different ages.
• Effects of corn silage derived from a genetically modified variety containing two transgenes on feed intake, milk production, and composition, and the absence of detectable transgenic deoxyribonucleic acid in milk in Holstein dairy cows.
• Enhanced synthesis of proinflammatory cytokines by vulvar vestibular fibroblasts: implications for vulvar vestibulitis.
• Evaluation of Bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs.
• Getting a piece of the pie? The economic boom of the 1990s and declining teen birth rates in the United States.
• Intrapartum group B streptococci prophylaxis in patients reporting a penicillin allergy.
• Optimization of retardance for a complete Stokes polarimeter.
• Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles.
• Physiological control of airway mucus secretion.
• Platelets as a novel target for PPARgamma ligands : implications for inflammation, diabetes, and cardiovascular disease.
• Pollutant-induced airway abnormalities.
• Quantitative measurement of anthrax toxin receptor messenger RNA in primary mononuclear phagocytes.
• Release of biologically active CD154 during collection and storage of platelet concentrates prepared for transfusion.
• Self-report of somatic symptoms in survivors of childhood cancer: effects of adaptive style.
• The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects.
• The peroxisome proliferator-activated receptor gamma (PPARgamma) ligands 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone induce human B lymphocyte and B cell lymphoma apoptosis by PPARgamma-independent mechanisms.
• The platelet as a therapeutic target for treating vascular diseases and the role of eicosanoid and synthetic PPARgamma ligands.
• The role of the clinical nurse specialist in promoting evidence-based practice and effecting positive patient outcomes.
• The use of Biobrane((R)) by burn units in the United Kingdom: A national study.
• [Not Available.]