Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells
| Autor: | Hyung-Ho Ha, Yong Jae Choi, Chathurika D.B. Gamage, So-Yeon Park, Rui Zhou, Young Hyun Yu, Kyung-Sub Moon, Tru Van Nguyen, İsa Taş, Kyung Keun Kim, Ji-Yoon Lee, Yi Yang, Hangun Kim, Sang Kyum Kim, Jin Han, Jae-Seoun Hur |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition Lichens Cell Survival Pharmaceutical Science Motility Antineoplastic Agents Apoptosis 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Drug Discovery Animals Humans Cytotoxic T cell MTT assay Viability assay Epithelial–mesenchymal transition beta Catenin Cell Proliferation 030304 developmental biology Pharmacology Mice Inbred BALB C 0303 health sciences Dose-Response Relationship Drug Chemistry Xenograft Model Antitumor Assays In vitro Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Complementary and alternative medicine Cell culture 030220 oncology & carcinogenesis Oxepins Cancer research Molecular Medicine Drug Screening Assays Antitumor Colorectal Neoplasms |
| Zdroj: | Phytomedicine. 56:10-20 |
| ISSN: | 0944-7113 |
| Popis: | Background Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms. Purpose The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells. Methods PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array in vitro as well as tumorigenicity study in vivo. Results PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated β-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity. Conclusion PHY suppresses the growth and motility of CRC cells via novel mechanisms. |
| Databáze: | OpenAIRE |
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