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

• Main Authors: Junyao Duan, Jing Shi, Xin Ma, Yundong Xuan, Pin Li, Hanfeng Wang, Yang Fan, Huijie Gong, Ling Wang, Yuewen Pang, Shaoqiang Pang, Yongji Yan
• Format: Article
• Language: English
• Published: Elsevier 2020-05-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: ccRCC; Esculetin; Proliferation; Cell cycle; Apoptosis; Migration
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332220302225

Background: 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. Methods: 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. Results: 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. Conclusion: 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.