Cancers, Vol. 12, Pages 599: Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas
Cancers, Vol. 12, Pages 599: Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas
Cancers doi: 10.3390/cancers12030599
Authors:
Sarkadi
Meszaros
Krencz
Canu
Krokker
Zakarias
Barna
Sebestyen
Papay
Hujber
Butz
Darvasi
Igaz
Doczi
Luconi
Chinopoulos
Patocs
Pheochromocytoma/paragangliomas (Pheo/PGL) are rare endocrine cancers with strong genetic background. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) predispose patients to malignant disease with limited therapeutic options and poor prognosis. Using a host of cellular and molecular biology techniques in 2D and 3D cell culture formats we show that SDH inhibition had cell line specific biological and biochemical consequences. Based on our studies performed on PC12 (rat chromaffin cell line), Hela (human cervix epithelial cell line), and H295R (human adrenocortical cell line) cells, we demonstrated that chromaffin cells were not affected negatively by the inhibition of SDH either by siRNA directed against SDHB or treatment with SDH inhibitors (itaconate and atpenin A5). Cell viability and intracellular metabolite measurements pointed to the cell line specific consequences of SDH impairment and to the importance of glutamate metabolism in chromaffin cells. A significant increase in glutaminase-1 (GLS-1) expression after SDH impairment was observed in PC12 cells. GLS-1 inhibitor BPTES was capable of significantly decreasing prolife...
Source: Cancers - Category: Cancer & Oncology Authors: Sarkadi Meszaros Krencz Canu Krokker Zakarias Barna Sebestyen Papay Hujber Butz Darvasi Igaz Doczi Luconi Chinopoulos Patocs Tags: Article Source Type: research
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