Honokiol, a Polyphenol Natural Compound, Attenuates Cisplatin-Induced Acute Cytotoxicity in Renal Epithelial Cells Through Cellular Oxidative Stress and Cytoskeleton Modulations

Cisplatinis a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatinadministration results in severe nephrotoxicityand impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalisexhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro. The protective effects of honokiolwere resulted from the combination of (1) reduced cellular oxidative stress ranging from 53%-32% reduction during a 24-hour incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells. By promoting the polymerization of actin (1.6-fold increase) and tubulin (1.8-fold increase) cytoskeleton, honokiolnot only maintained epithelial cell morphology, but also stabilized cellular localizations of tight junction protein Occludinand adhesion junction protein E-Cadherin. With stabilized junction protein complexes and structural polymerized cytoskeleton network, honokiolpreserved epithelial cell polarityand morphology and thus reduced cisplatin-induced cell disruptionand damages. Our data demonstrated for the first time that honokiolcould counteract with cisplatin-induced damages in renal epithelial cells in vitro, future in vivo studies would further validate the potential clinical application of honokiolin cisplatin-based cancer treatments with reduced nephrotoxicity.