Esculetin inhibits proliferation, migration, and invasion of clear cell renal cell carcinoma cells

Esculetin inhibits proliferation, migration, and invasion of clear cell renal cell carcinoma cells

•Esculetin inhibits clear cell renal cell carcinoma growth in a dose- and time-dependent manner.•Esculetin induces cell cycle arrest and apoptosis.•Esculetin represses cell migration and invasion by reversing epithelial mesenchymal transition. Esculetin, the main active ingredient in the Chinese her...

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Published in:Biomedicine & pharmacotherapy Vol. 125; p. 110031
Main Authors: Duan, Junyao, Shi, Jing, Ma, Xin, Xuan, Yundong, Li, Pin, Wang, Hanfeng, Fan, Yang, Gong, Huijie, Wang, Ling, Pang, Yuewen, Pang, Shaoqiang, Yan, Yongji
Format: Journal Article
Language:English
Published: France Elsevier Masson SAS 01-05-2020
Elsevier
Subjects:
Apoptosis
ccRCC
Cell cycle
Esculetin
Invasion
Migration
Proliferation
ccRCC
Migration
Cell cycle
Esculetin
Proliferation
Invasion
Apoptosis
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Summary:•Esculetin inhibits clear cell renal cell carcinoma growth in a dose- and time-dependent manner.•Esculetin induces cell cycle arrest and apoptosis.•Esculetin represses cell migration and invasion by reversing epithelial mesenchymal transition. Esculetin, the main active ingredient in the Chinese herbal medicineCortex Fraxini, has been shown to possess antitumor activity. However, the effect of esculetin on clear cell renal cell carcinoma (ccRCC) has not been investigated. MTS assays and colony formation assays were used to study the cytotoxicity of esculetin. The effects of esculetin on cell cycle and apoptosis were analyzed by flow cytometry. Western blot was used to detect cell cycle-, apoptosis-, and EMT-related proteins. Wound-healing assays and transwell assays were performed to study the effect of esculetin on cell migration and invasion in the ccRCC cell lines 786-O and SN12-PM6. Esculetin exerted cytotoxic activities in 786-O and SN12-PM6 cells in a dose- and time-dependent manner. The compound arrested the cell cycle in G0/G1 and G2/M phase with down-regulation of Cyclin D1, CDK4, CDK6, and c-Myc expression. Esculetin also induced apoptosis and the expression of cleaved caspase 3 increased. Additionally, esculetin significantly inhibited 786-O and SN12-PM6 cell migration and invasion, the expression of E-Cadherin increased, and the expression of N-cadherin and vimentin decreased. Taken together, these results suggest that esculetin inhibits proliferation, migration, and invasion of ccRCC and is a potential novel therapeutic agent for the treatment of ccRCC.
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ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2020.110031