Oncotarget

Research Papers:

Pharmacological targeting of ROS reaction network in myeloid leukemia cells monitored by ultra-weak photon emission

Rosilene Cristina Rossetto Burgos, Rawi Ramautar, Eduard P.A. van Wijk, Thomas Hankemeier, Jan van der Greef and Alireza Mashaghi _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:2028-2034. https://doi.org/10.18632/oncotarget.23175

Metrics: PDF 478 views  |   HTML 1374 views  |   ?  


Abstract

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

Correspondence to:

Alireza Mashaghi, email: a.mashaghi.tabari@lacdr.leidenuniv.nl

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

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23175