Multiple Targets of 3-Dehydroxyceanothetric Acid 2-Methyl Ester to Protect Against Cisplatin-Induced Cytotoxicity in Kidney Epithelial LLC-PK1 Cells.
Dahae LeeKi Hyun KimWon-Yung LeeChang-Eop KimSang Hyun SungKyo-Bin KangKi Sung KangPublished in: Molecules (Basel, Switzerland) (2019)
Chronic exposure to cisplatin, a potent anticancer drug, causes irreversible kidney damage. In this study, we investigated the protective effect and mechanism of nine lupane- and ceanothane-type triterpenoids isolated from jujube (Ziziphus jujuba Mill., Rhamnaceae) on cisplatin-induced damage to kidney epithelial LLC-PK1 cells via mitogen-activated protein kinase (MAPK) and apoptosis pathways. Cisplatin-induced LLC-PK1 cell death was most significantly reduced following treatment with 3-dehydroxyceanothetric acid 2-methyl ester (3DC2ME). Additionally, apoptotic cell death was significantly reduced. Expression of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 was markedly suppressed by 3DC2ME, indicating inhibition of the MAPK pathway. Treatment with 3DC2ME also significantly reduced expression of active caspase-8 and -3, Bcl-2-associated X protein (Bax), and B cell lymphoma 2 (Bcl-2), indicating the inhibition of apoptosis pathways in the kidneys. We also applied the network pharmacological analysis and identified multiple targets of 3DC2ME related to MAPK signaling pathway and apoptosis.
Keyphrases
- cell cycle arrest
- cell death
- signaling pathway
- pi k akt
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- dendritic cells
- poor prognosis
- cell proliferation
- epithelial mesenchymal transition
- protein kinase
- tyrosine kinase
- drug induced
- emergency department
- replacement therapy
- anti inflammatory
- network analysis