Antiglioma activity of 2,2':6',2"-terpyridineplatinum(II) complexes in a rat model--effects on cellular redox metabolism

Free Radical Biology & Medicine
Rezvan AhmadiKatja Becker

Abstract

The mammalian thioredoxin system, comprising the selenoenzyme thioredoxin reductase (TrxR) and the 12-kDa protein thioredoxin (Trx), is implicated in thiol-mediated antioxidant defense and redox regulatory processes including transcriptional control, DNA synthesis, and apoptosis. Cell proliferation supported by the thioredoxin system can be suppressed by TrxR inhibition. In this study, we assessed the effects of the potent hTrxR inhibitors 4-mercaptopyridine (4'-chloro-2,2':6',2"-terpyridine)platinum nitrate (I(23)2N) and 2-mercaptopyridine (4'-chloro-2,2':6',2"-terpyridine)platinum nitrate (I(25)2N) on glioblastoma in a rat model. These compounds show no or little cross-resistance with cisplatin and are thus of great clinical interest. Triple intravenous application of 25-35 mg/kg of the compounds led to a significant decrease of tumor growth as determined by magnetic resonance imaging. Metabolic as well as redox parameters in the blood of the animals were not altered. However, TrxR activity was significantly decreased in the tumor tissue, and redox parameters-including glutathione concentrations, total antioxidant status, and the activities of different antioxidant enzymes-showed tissue-specific variations. As indicated by di...Continue Reading

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Citations

Feb 1, 2011·Antioxidants & Redox Signaling·Ute JungwirthPetra Heffeter
Nov 19, 2008·Antimicrobial Agents and Chemotherapy·Nicole SturmKatja Becker
Jul 18, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Valentina Gandin, Aristi P Fernandes
Jan 12, 2010·Chemistry : a European Journal·Niculina D BogdanDaniel P Funeriu
Jan 17, 2015·Brain Tumor Pathology·Hasan EsenLutfi Saltuk Demir
Oct 24, 2006·Seminars in Cancer Biology·Sabine Urig, Katja Becker
Jun 16, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Giarita FerraroAntonello Merlino
Feb 2, 2019·Current Medicinal Chemistry·Vasco BrancoCristina Carvalho
Nov 14, 2014·Journal of Neuro-oncology·Hasan EsenLutfi Saltuk Demir
Aug 4, 2009·Journal of Agricultural and Food Chemistry·Li-Ching ChenWen-Sen Lee

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