%0 Journal Article
%T Inhibition of Gap Junctions Sensitizes Primary Glioblastoma Cells for Temozolomide
%A Andreas Dolf
%A Andreas Waha
%A Anna-Laura Potthoff
%A Bernd O. Evert
%A Dieter Henrik Heiland
%A Erdem G¨¹resir
%A Filipe Rodrigues Almeida
%A Hartmut Vatter
%A Kevin Joseph
%A Matthias Schneider
%A Mike-Andrew Westhoff
%A Patrick Schuss
%A Simon P. Behringer
%A Torsten Pietsch
%A Ulrich Herrlinger
%A ¨¢gi G¨¹resir
%J Archive of "Cancers".
%D 2019
%R 10.3390/cancers11060858
%X Gap junctions have recently been shown to interconnect glioblastoma cells to a multicellular syncytial network, thereby allowing intercellular communication over long distances as well as enabling glioblastoma cells to form routes for brain microinvasion. Against this backdrop gap junction-targeted therapies might provide for an essential contribution to isolate cancer cells within the brain, thus increasing the tumor cells¡¯ vulnerability to the standard chemotherapeutic agent temozolomide. By utilizing INI-0602¡ªa novel gap junction inhibitor optimized for crossing the blood brain barrier¡ªin an oncological setting, the present study was aimed at evaluating the potential of gap junction-targeted therapy on primary human glioblastoma cell populations. Pharmacological inhibition of gap junctions profoundly sensitized primary glioblastoma cells to temozolomide-mediated cell death. On the molecular level, gap junction inhibition was associated with elevated activity of the JNK signaling pathway. With the use of a novel gap junction inhibitor capable of crossing the blood¨Cbrain barrier¡ªthus constituting an auspicious drug for clinical applicability¡ªthese results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research
%K glioblastoma
%K gap junctions
%K INI-0602
%K cell death
%K c-Jun
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628126/