Pharmacological targeting of ROS reaction network in myeloid leukemia cells monitored by ultra-weak photon emission
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Rosilene Cristina Rossetto Burgos1,2, Rawi Ramautar1, Eduard P.A. Van Wijk2, Thomas Hankemeier1, Jan Van Der Greef1,2 and Alireza Mashaghi1
1Leiden Academic Centre for Drug Research, Faculty of Mathematics and Natural Sciences, Leiden University, 2300 RA Leiden, The Netherlands
2Sino-Dutch Centre for Preventive and Personalized Medicine/Centre for Photonics of Living Systems, Leiden University, 2300 RA Leiden, The Netherlands
Alireza Mashaghi, email: [email protected]
Keywords: reactive oxygen species; ultra-weak photon emission; NADPH oxidase; myeloperoxidase; pharmacological inhibitors
Received: August 08, 2016 Accepted: November 20, 2017 Published: December 11, 2017
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.
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