Unique Triterpenoid of Jujube Root Protects Cisplatin-induced Damage in Kidney Epithelial LLC-PK1 Cells via Autophagy Regulation

Nutrients. 2020 Mar 2;12(3):677. doi: 10.3390/nu12030677.

Abstract

Chronic exposure to cisplatin is associated with irreversible kidney impairment. In this present study, we explored the protective effects of 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME) isolated from roots of jujube (Ziziphus jujuba, Rhamnaceae) against cisplatin-induced damage in vitro. In kidney epithelial LLC-PK1 cells, western blotting and staining with specific autophagy epifluorescent dye CytoID were used to determine the molecular pathways involving autophagy. Treatment with 3DC2ME reduced the increased Cyto-ID-stained autophagic vesicles and reversed the protein expressions of 5' AMP-activated protein kinase subunit β-1 (AMPK)/mammalian target of rapamycin (mTOR)-dependent signaling pathway in cisplatin-induced cell death. Additionally, treatment with autophagy inhibitor 3-methyladenine (3-MA) and with or without 3DC2ME attenuated the cisplatin-induced apoptosis. Although further research is necessary to substantiate the effects, we evaluated the potential mechanism of action of 3DC2ME as an adjuvant for cancer patients.

Keywords: Ziziphus jujuba; autophagy; cisplatin; nephrotoxicity.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Autophagy / drug effects*
  • Cell Line
  • Cisplatin / adverse effects*
  • Cisplatin / pharmacology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Kidney / metabolism*
  • Kidney / pathology
  • Plant Roots / chemistry*
  • Swine
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Ziziphus / chemistry*

Substances

  • Triterpenes
  • Cisplatin