Antineoplastic XXXX coordinated complexes (Casiopeinas) uncouple oxidative phosphorylation and induce mitochondrial permeability transition in @entity299 and cardiomyocytes.

@entity1708 @entity2125 @entity5568 @entity4588 @entity205 @entity1432 @entity920 @entity299 @entity1370
UNASSIGNED: @entity920 -based drugs, Casiopeinas (Cas), exhibit antiproliferative and antineoplastic activities in vitro and in vivo, respectively. Unfortunately, the clinical use of these novel chemotherapeutics could be limited by the development of dose-dependent @entity1370 . In addition, the molecular mechanisms underlying Cas @entity1370 and anticancer activity are not completely understood. Here, we explore the potential impact of Cas on the @entity299 energetics as the molecular mechanisms underlying Cas-induced @entity1370 . To explore the properties on mitochondrial metabolism, we determined Cas effects on respiration, membrane potential, membrane permeability, and redox state in isolated @entity299 . The effect of Cas on the mitochondrial membrane potential (    m) was also evaluated in isolated cardiomyocytes by confocal microscopy and flow cytometry. Cas IIIEa, IIgly, and IIIia predominately inhibited maximal @entity2125 - and @entity4588 -linked mitochondrial respiration, increased the state-4 respiration rate and reduced membrane potential, suggesting that Cas also act as mitochondrial uncouplers. Interestingly, @entity205 inhibited Cas-induced mitochondrial depolarization, suggesting the involvement of mitochondrial permeability transition pore (mPTP). Similarly to isolated mitochondria, in isolated cardiomyocytes, Cas treatment decreased the     m and @entity205 treatment prevented mitochondrial depolarization. The production of @entity5568 increased in Cas-treated mitochondria, which might also increase the oxidation of mitochondrial proteins such as @entity1708 translocase. In accordance, an antioxidant scavenger (Tiron) significantly diminished Cas IIIia mitochondrial depolarization. Cas induces a prominent loss of membrane potential, associated with alterations in redox state, which increases mPTP opening, potentially due to @entity1432 -dependent modifications of the pore, suggesting that direct or indirect inhibition of mPTP opening might reduce Cas-induced @entity1370 .
