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© 2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

[...]BET proteins mediate protein–protein interaction networks between diverse arrays of partners, and function as mitosis bookmarks, protein scaffolds and chromatin regulators in cellular processes; controlling proliferation and cell cycle progression. BETi like JQ1 and I-BET-151, a highly specific and potent inhibitor of BRD2/3/4 [4,5], have shown encouraging activity in multiple preclinical models of medulloblastoma [2], prostate cancer [6], NUT midline carcinoma (NMC), T-Cell Acute Lymphoblastic Leukemia (T-ALL) [7], ovarian cancer [8], drug resistant myeloma [9,10], uveal melanoma [11], breast cancer cells [12], hepatocellular carcinoma [13], Ewing sarcoma [14,15], and gastric cancer [16], among others (please see the review from French Cancer Agency [17] for a recent overview of the BETi in preclinical models). Since numerous anticancer drugs have been correlated to cardiomyopathy [18,19], and since BETi can affect non-cancerous tissues, we aimed to investigate any ultrastructural alterations of the heart induced by BETi in healthy animals. [...]we did not observe inflammatory infiltrates nor ultrastructural features of apoptosis in our sections [21]. Nonetheless, accurate quantification of these changes was difficult in the absence of 3D reconstruction by tomography. [...]the spaces between mitochondria were extensively enlarged (Figure 2H).

Details

Title
The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats
Author
Piquereau, Jérôme; Boet, Angèle; Péchoux, Christine; Antigny, Fabrice; Lambert, Mélanie; Gressette, Mélanie; Ranchoux, Benoît; Gambaryan, Natalia; Domergue, Valérie; Mumby, Sharon; Montani, David; Adcock, Ian M; Humbert, Marc; Garnier, Anne; Rucker-Martin, Catherine; Perros, Frédéric
Publication year
2019
Publication date
2019
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2332255147
Copyright
© 2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.