Endothelin B receptor antagonists block proliferation and induce apoptosis in glioma cells

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Mayra PaolilloSergio Schinelli

Abstract

The proliferative and antiapoptotic actions of endothelin (ET)-1 in cancer cells have been documented and ET receptor antagonists have been exploited as potential anticancer drugs. Glioblastoma cell lines express both ETA and ETB receptors and previous works have shown that ETB receptors are involved in the proliferation of different cancer cell types. In this study we have investigated the effects of two structurally unrelated ETB receptor antagonists, BQ788 and A192621, on cell survival, proliferation and apoptosis in 1321-N1, U87 and IPDDCA2 glioma cell lines. BQ788 and A192621 reduced glioma cells viability and proliferation assessed by BrdU incorporation and cell cycle analysis by flow cytometry, while in contrast the ETA receptor antagonist BQ123 had no effect on cell survival. TUNEL assay and immunocytochemical experiments showed that BQ788 and A192621 trigger apoptotic processes mainly via activation of the intrinsic mitochondrial pathway involving caspase-9 activation, AIF release and cytochrome c translocation. Furthermore, treatment with ETB antagonists downregulates ERK- and p38MAPK-dependent pathways but does not affect VEGF mRNA levels. Our findings support the hypothesis that ETB antagonists represent a new promi...Continue Reading

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Citations

Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Matthew D LeComteJeffrey L Spees
Jan 22, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Rong Wang, Roderick H Dashwood
Jan 15, 2011·British Journal of Pharmacology·A BagnatoJ Growcott
Jan 13, 2015·Journal of Clinical Pathology·N CookP G Corrie
May 3, 2016·Progress in Neurobiology·Stéphanie HostenbachJacques De Keyser
Jun 9, 2016·Journal of Medicinal Chemistry·John-David Aubert, Lucienne Juillerat-Jeanneret
Jun 10, 2017·British Journal of Haematology·Anna RussignanCristina Tecchio
Jul 22, 2017·Canadian Journal of Physiology and Pharmacology·Marianne MikhailGhassan Bkaily
Apr 21, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·S RichardL Motte

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