Inhibition of gap junctions sensitizes primary glioblastoma cells for temozolomide

Potthoff AL, Heiland DH, Evert BO, Almeida FR, Behringer SP, Dolf A, Güresir Á, Güresir E, Joseph K, Pietsch T, Schuss P, Herrlinger U, Westhoff MA, Vatter H, Waha A, Schneider M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Cancers MDPI

Book Volume: 11

Article Number: 858

Journal Issue: 6

DOI: 10.3390/cancers11060858

Abstract

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—a novel gap junction inhibitor optimized for crossing the blood brain barrier—in 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–brain barrier—thus constituting an auspicious drug for clinical applicability—these results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research.

Authors with CRIS profile

Dieter Henrik Heiland

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE)

How to cite

APA:

Potthoff, A.L., Heiland, D.H., Evert, B.O., Almeida, F.R., Behringer, S.P., Dolf, A.,... Schneider, M. (2019). Inhibition of gap junctions sensitizes primary glioblastoma cells for temozolomide. Cancers, 11(6). https://doi.org/10.3390/cancers11060858

MLA:

Potthoff, Anna Laura, et al. "Inhibition of gap junctions sensitizes primary glioblastoma cells for temozolomide." Cancers 11.6 (2019).

BibTeX: Download