Junyao Duan1, Jing Shi1, Xin Ma2, Yundong Xuan2, Pin Li3, Hanfeng Wang2, Yang Fan2, Huijie Gong1, Ling Wang1, Yuewen Pang1, Shaoqiang Pang1, Yongji Yan4. 1. Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China. 2. Department of Urology, Chinese PLA General Hospital, Beijing, China. 3. Department of Pediatric Urology, Bayi Children's Hospital Affiliated to PLA General Hospital, Beijing, China. 4. Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China. Electronic address: yyjdzm@163.com.
Abstract
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.
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.
Authors: Essa M Bajalia; Farah B Azzouz; Danielle A Chism; Derrek M Giansiracusa; Carina G Wong; Kristina N Plaskett; Anupam Bishayee Journal: Cancers (Basel) Date: 2022-07-04 Impact factor: 6.575