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Pharmacological targeting of ROS reaction network in myeloid leukemia cells monitored by ultra-weak photon emission
- Source :
- Oncotarget, Oncotarget, 9(2), 2028-2034
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- Acute myeloid leukemia (AML) is a blood cancer that is caused by a disorder of the process that normally generates neutrophils. Function and dysfunction of neutrophils are key to physiologic defense against pathogens as well as pathologies including autoimmunity and cancer. A major mechanism through which neutrophils contribute to health and disease is oxidative burst, which involves rapid release of reactive oxygen species (ROS) generated by a chemical reaction network catalyzed by enzymes including NADPH oxidase and myeloperoxidase (MPO). Due to the involvement of neutrophil-derived reactive oxygen species in many diseases and importance of NADPH oxidase and MPO-mediated reactions in progression and treatment of myeloid leukemia, monitoring this process and modulating it by pharmacological interventions is of great interest. In this work, we have evaluated the potential of a label-free method using ultra-weak photon emission (UPE) to monitor ROS production in neutrophil-like HL60 myeloid leukemia cells. Suppression of ROS was achieved by several drug candidates that target different parts of the reaction pathway. Our results show that UPE can report on ROS production as well as suppression by pharmacological inhibitors. We find that UPE is primarily generated by MPO catalyzed reaction and thus will be affected when an upstream reaction is pharmacologically modulated.
- Subjects :
- HL60
ultra-weak photon emission
medicine.disease_cause
Autoimmunity
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
reactive oxygen species
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
biology
Myeloid leukemia
pharmacological inhibitors
Respiratory burst
myeloperoxidase
Enzyme
Oncology
chemistry
030220 oncology & carcinogenesis
Myeloperoxidase
biology.protein
Cancer research
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....042d538ff5c4f68118d157fd298008f3