Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met
- PDF / 7,206,401 Bytes
- 17 Pages / 595.22 x 842 pts (A4) Page_size
- 33 Downloads / 151 Views
779
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) ISSN 1673-1581 (Print); ISSN 1862-1783 (Online) www.jzus.zju.edu.cn; www.springerlink.com E-mail: [email protected]
Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met* Qian-qian LIU§1, Xue-li ZENG§2, Yue-lin GUAN2, Jing-xin LU2, Kai TU2, Fei-yan LIU†‡2 1 2
Deparement of Internal Medicine, Zhejiang University Hospital, Hangzhou 310027, China
Research Centre of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou 310058, China †
E-mail: [email protected]
Received Apr. 20, 2020; Revision accepted Aug. 16, 2020; Crosschecked Sept. 9, 2020
Abstract: Verticillin A is a diketopiperazine compound which was previously isolated from Amanita flavorubescens Alk (containing parasitic fungi Hypomyces hyalines (Schw.) Tul.). Here, we initially found, by wound healing assay and Transwell assay in vitro, that verticillin A possesses an inhibitory effect against the migration and invasion of the human colon cancer cell. Subsequently, c-mesenchymal-epithelial transition factor (c-Met) was identified as a molecular target of verticillin A by screening key genes related to cell migration. Verticillin A-mediated c-Met suppression is at the transcriptional level. Further study demonstrated that verticillin A suppressed c-MET phosphorylation and decreased c-MET protein level. In addition, verticillin A inhibited the phosphorylation of c-MET downstream molecules including rat sarcoma (Ras)-associated factor (Raf), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT). Overexpression of Erk partially reversed the verticillin A-mediated anti-metastasis action in the human colon cancer cell. More importantly, verticillin A also inhibited cancer cell metastasis in vivo. Thus, verticillin A can significantly inhibit the migration and invasion of colon cancer cells by targeting c-Met and inhibiting Ras/Raf/mitogen-activated extracellular signal-regulated kinase (MEK)/ERK signaling pathways. Therefore, we determined that verticillin A is a natural compound that can be further developed as an anti-metastatic drug in human cancers. Key words: Verticillin A; Colon cancer; Migration; Invasion; c-Mesenchymal-epithelial transition factor (c-MET) https://doi.org/10.1631/jzus.B2000190 CLC number: R73-37
1 Introduction Colorectal cancer (CRC) is the third-most common type of cancer and the third leading cause of cancer-associated mortality worldwide (Lino-Silva et al., 2019). There are four main treatments for colon cancer patients: chemotherapy, radiotherapy, surgery, and targeted therapy (Engstrom, 2012). The corner‡
Corresponding author The two authors contributed equally to this work * Project supported by the Zhejiang Provincial Natural Science Foundation of China (No. LY20H160039), the National Natural Science Foundation of China (No. 31570811), and the Siyuan Foundation, Hongkong, China ORCID: Fei-yan LIU, https://orcid.org/0000-0003-1007-1366 © Zhejiang University and Spri
Data Loading...
