Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells

• Published in: Phytomedicine (Stuttgart) 2019-03, Vol.56, p.10-20
• Main Authors: Taş, İsa, Han, Jin, Park, So-Yeon, Yang, Yi, Zhou, Rui, Gamage, Chathurika D.B., Van Nguyen, Tru, Lee, Ji-Yoon, Choi, Yong Jae, Yu, Young Hyun, Moon, Kyung-Sub, Kim, Kyung Keun, Ha, Hyung-Ho, Kim, Sang Kyum, Hur, Jae-Seoun, Kim, Hangun
• Format: Article
• Language: English
• Subjects: Animals; Anticancer; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; beta Catenin - genetics; beta Catenin - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Transformation, Neoplastic - genetics; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; CRC; dimethylsulfoxide; DMSO; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; EMT; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Lichen; Lichens - chemistry; Male; Mice, Inbred BALB C; Motility; Natural product; Oxepins - administration & dosage; Oxepins - pharmacokinetics; Oxepins - pharmacology; PHY; physciosporin; thin-layer chromatography; TLC; Tumourigenesis; Xenograft Model Antitumor Assays
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2018.09.219

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. The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells. 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. 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. PHY suppresses the growth and motility of CRC cells via novel mechanisms. [Display omitted]