Sodium Ferulate Prevents Daunorubicin - Induced Apoptosis in H9c2 Cells via Inhibition of the ERKs Pathway

• Published in: Cellular physiology and biochemistry Vol. 36; no. 6; pp. 2121 - 2136
• Main Authors: Wu, Zhi-Juan, Yu, Jing, Fang, Qiu-Juan, Wang, Rui-Xing, Lian, Jia-Bian, He, Rui-Lan, Jiao, Hai-Xia, Lin, Mo-Jun
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.08.2015
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Benzimidazoles - pharmacology; Cardio-protection; Caspase 9 - metabolism; Cell Line; Cell Shape - drug effects; Cell Survival - drug effects; Coumaric Acids - pharmacology; Cytochromes c - metabolism; Daunorubicin; Daunorubicin - adverse effects; Enzyme Activation - drug effects; ERKs; Extracellular Signal-Regulated MAP Kinases - metabolism; H9c2 cell; HL-60 Cells; Humans; Inhibitory Concentration 50; K562 Cells; MAP Kinase Signaling System - drug effects; Membrane Potential, Mitochondrial - drug effects; Original Paper; Phosphorylation - drug effects; Proteolysis - drug effects; Rats; Sodium Ferulate; Troponin I - metabolism; Tubulin - metabolism; Sodium Ferulate; Daunorubicin; H9c2 cell; ERKs; Cardio-protection; Apoptosis
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000430179

Background: Daunorubicin (DNR)-induced cardiotoxicity, which is closely associated with cardiomyocyte apoptosis, limits the drug's clinical application. The activation of the extracellular regulated protein kinases (ERKs) pathway is responsible for the pro-apoptosis effect of DNR Sodium ferulate (SF) has recently been found to attenuate both DNR-induced cardiotoxicity and mitochondrial apoptosis in juvenile rats. Nonetheless, the precise mechanism underlying SF-induced cardio-protection remains unclear. Methods: The DNR-injured H9c2 cell model was prepared by incubating the cells in 1 µM DNR for 24 h. Amounts of 15.6, 31.3 or 62.5 µM SF were simultaneously added to the cells. The effect of SF on the cytotoxic and apoptotic parameters of the cells was studied by monitoring apoptosis regulation via the ERKs pathway. Results: SF attenuated DNR-induced cell death (particularly apoptotic death), cTnI and β-tubulin degradation, and cellular morphological changes. SF reduced mitochondrial membrane potential depolarization, cytochrome c leakage, and caspase-9 and caspase-3 activation. SF also decreased ERK1/2, phospho-ERK1/2, p53 and Bax expression and increased Bcl-2 expression. These effects were similar to the results observed when using the pharmacological ERKs phosphorylation inhibitor, AZD6244. Conclusion: We determined that SF protects H9c2 cells from DNR-induced apoptosis through a mechanism that involves the interruption of the ERKs signaling pathway.