Data from Nongenomic Effects of Cisplatin: Acute Inhibition of Mechanosensitive Transporters and Channels without Actin Remodeling

• DOI: 10.1158/0008-5472.c.6500913.v1
• Publication Date: 2024-03-12T19:21:45Z
• Authors: Nina Milosavljevic; Christophe Duranton; Nadir Djerbi; Pierre Henri Puech; Pierre Gounon; Dominique Lagadic...; Marie Thérèse Dim...; Cyril Rauch; Michel Tauc; Laurent Counillon; Mallorie Poët

<div>Abstract<p>Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range short-term side effects that are unlikely be related its genomic action. As cisplatin has been shown modify membrane properties in different systems, we investigated on mechanosensitive ion transporters and channels. We show here noncompetitive inhibitor Na<sup>+</sup>/H<sup>+</sup> exchanger NHE-1, with half-inhibition concentration 30 μg/mL associated decrease <i>V</i><sub>max</sub> Hill coefficient. also showed blocks Cl<sup>−</sup> K<sup>+</sup> channels VSORC TREK-1 at similar concentrations. contrast, nonmechanosensitive CFTR TASK-1 Na<sup>+</sup>-coupled glucose transport, which share functional features VSORC, TREK-1, respectively, were insensitive cisplatin. next whether action was due direct effect or cortical actin remodeling would affect mechanosensors. Using scanning electron microscopy, <i>in vivo</i> labeling, atomic force did not observe any modification Young's modulus cytoskeleton for up 60 120 cisplatin, whereas these concentrations modified morphology. Our results reveal novel mechanism affects involved fate programs and/or expressed organs elicits strong secondary effects, such as inner ear peripheral nervous system. These might constitute common denominator previously unrelated this drug. Cancer Res; 70(19); 7514–22. ©2010 AACR.</p></div>