2. Academic Validation
  3. Aucubin protects mouse cochlear hair cells from cisplatin-induced ototoxicity via activation of the PI3K/AKT/STAT3 pathway

Aucubin protects mouse cochlear hair cells from cisplatin-induced ototoxicity via activation of the PI3K/AKT/STAT3 pathway

  • Biochem Pharmacol. 2023 Jan 28;115440. doi: 10.1016/j.bcp.2023.115440.
Yumeng Jiang 1,  Zhuangzhuang Li 1,  Qiang Ma 1,  Wenqi Dong 1,  Qingxiu Yao 2,  Dongzhen Yu 3
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China.
  • 2 Department of Otolaryngology The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China. Electronic address: drqxyao@126.com.
  • 3 Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China; Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, China; Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, 200233, China. Electronic address: 7250012023@shsmu.edu.cn.
PMID: 36720354 DOI: 10.1016/j.bcp.2023.115440
Abstract

Cisplatin is commonly used to treat cancers and is associated with a significant risk of irreversible sensorineural hearing loss (HL). However, no effective preventive strategies are available for cisplatin-induced HL. Therefore, significant efforts have been made to discover new drugs protecting cochlear hair cells (HCs) from cisplatin-induced damage. We found that a new phytochemical, aucubin, attenuated cisplatin-induced Apoptosis, the production of Reactive Oxygen Species, and mitochondrial dysfunction in House Ear Institute-Organ of Corti 1 cells and cochlear HCs. Moreover, aucubin attenuated cisplatin-induced sensorineural HL and HC loss in vivo. Furthermore, RNA sequencing analysis revealed that the otoprotective effects of aucubin were mainly mediated by increased STAT3 phosphorylation via the PI3K/Akt pathway. Inhibition of the STAT3 signaling pathway with the inhibitor S3I-201 or siRNA disrupted the protective effects of aucubin on cisplatin-induced Apoptosis. In conclusion, we identified an otoprotective effect of aucubin. Therefore, aucubin could be used to prevent cisplatin-induced ototoxicity.

Keywords

Ototoxicity; PI3K/AKT; aucubin; cisplatin; p-STAT3.

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