Florence Lefranc1, Robert Kiss. 1. Department of Neurosurgery, Erasme University Hospital,Université Libre de Bruxelles, Brussels, Belgium. fllefran@ulb.ac.be
Abstract
PURPOSE: To review the involvement of the ion transporter Na+/K+-ATPase (NaK) in the migration and proliferation of glioma cells. Preliminary studies indicate that NaK alpha1 subunits seem to be upregulated in a proportion of glioblastomas but not in normal brain tissues. DESIGN: The present review focuses on (1) the natural resistance of migrating malignant glioma cells to apoptosis, (2) autophagic cell death as an alternative to combat malignant gliomas, (3) the fact that reducing the levels of malignant glioma cell motility can restore proapoptotic drug sensitivity,and (4) on the observation that inhibiting the NaK activity reduces both glioma cell proliferation and migration. RESULTS: The natural ligands of the NaK are the cardiotonic steroids. A hemisynthetic derivative of 2"-oxovoruscharin (UNBS1450), a novel cardenolide, displays unique structural features, making its binding affinity to NaK alpha subunits (including alpha1) 10 to 100 times higher than that of other cardenolides. UNBS1450 markedly decreases intracellular ATP concentration in glioma cells, disorganizes the actin cytoskeleton, and leads to autophagic cell death in NaK alpha1 over-expressing glioma cells. CONCLUSIONS: Glioblastoma patients who do not respond to chemotherapy and whose tumors over-express NaK alpha1 subunits could benefit from a treatment using ligands with marked binding affinity for the NaK alpha1 subunit.
PURPOSE: To review the involvement of the ion transporter Na+/K+-ATPase (NaK) in the migration and proliferation of glioma cells. Preliminary studies indicate that NaK alpha1 subunits seem to be upregulated in a proportion of glioblastomas but not in normal brain tissues. DESIGN: The present review focuses on (1) the natural resistance of migrating malignant glioma cells to apoptosis, (2) autophagic cell death as an alternative to combat malignant gliomas, (3) the fact that reducing the levels of malignant glioma cell motility can restore proapoptotic drug sensitivity,and (4) on the observation that inhibiting the NaK activity reduces both glioma cell proliferation and migration. RESULTS: The natural ligands of the NaK are the cardiotonic steroids. A hemisynthetic derivative of 2"-oxovoruscharin (UNBS1450), a novel cardenolide, displays unique structural features, making its binding affinity to NaK alpha subunits (including alpha1) 10 to 100 times higher than that of other cardenolides. UNBS1450 markedly decreases intracellular ATP concentration in glioma cells, disorganizes the actin cytoskeleton, and leads to autophagic cell death in NaK alpha1 over-expressing glioma cells. CONCLUSIONS:Glioblastomapatients who do not respond to chemotherapy and whose tumors over-express NaK alpha1 subunits could benefit from a treatment using ligands with marked binding affinity for the NaK alpha1 subunit.
Authors: V Senner; S Schmidtpeter; S Braune; S Püttmann; S Thanos; U Bartsch; M Schachner; W Paulus Journal: Neuropathol Appl Neurobiol Date: 2003-08 Impact factor: 8.090
Authors: Cromwell E Espineda; Jay H Chang; Jeffery Twiss; Sigrid A Rajasekaran; Ayyappan K Rajasekaran Journal: Mol Biol Cell Date: 2003-12-29 Impact factor: 4.138
Authors: Anna M Joy; Christian E Beaudry; Nhan L Tran; Francisco A Ponce; David R Holz; Tim Demuth; Michael E Berens Journal: J Cell Sci Date: 2003-09-16 Impact factor: 5.285
Authors: Christian E Badr; Thomas Wurdinger; Jonas Nilsson; Johanna M Niers; Michael Whalen; Alexei Degterev; Bakhos A Tannous Journal: Neuro Oncol Date: 2011-07-13 Impact factor: 12.300
Authors: Antonio Evidente; Alexander Kornienko; Florence Lefranc; Alessio Cimmino; Ramesh Dasari; Marco Evidente; Véronique Mathieu; Robert Kiss Journal: Curr Med Chem Date: 2015 Impact factor: 4.530
Authors: Diogo G Garcia; Lidia M F Amorim; Mauro V de Castro Faria; Aline S Freire; Ricardo E Santelli; Clóvis O Da Fonseca; Thereza Quirico-Santos; Patricia Burth Journal: Mol Cell Biochem Date: 2010-08-06 Impact factor: 3.396
Authors: Aleksandra M Bondžić; Mirjana B Čolović; Goran V Janjić; Božidarka Zarić; Sandra Petrović; Danijela Z Krstić; Tiziano Marzo; Luigi Messori; Vesna M Vasić Journal: J Biol Inorg Chem Date: 2017-04-21 Impact factor: 3.358
Authors: Oliver D Mrowczynski; Alexandre J Bourcier; Jason Liao; Sara T Langan; Charles S Specht; Elias B Rizk Journal: J Neurooncol Date: 2018-01-25 Impact factor: 4.130
Authors: Andrea Perne; Markus K Muellner; Magdalena Steinrueck; Nils Craig-Mueller; Julia Mayerhofer; Ilse Schwarzinger; Mathew Sloane; Iris Z Uras; Gregor Hoermann; Sebastian M B Nijman; Matthias Mayerhofer Journal: PLoS One Date: 2009-12-16 Impact factor: 3.240