İsa Taş1, Jin Han2, So-Yeon Park2, Yi Yang1, Rui Zhou2, Chathurika D B Gamage1, Tru Van Nguyen2, Ji-Yoon Lee3, Yong Jae Choi3, Young Hyun Yu2, Kyung-Sub Moon4, Kyung Keun Kim5, Hyung-Ho Ha2, Sang Kyum Kim3, Jae-Seoun Hur6, Hangun Kim7. 1. Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea; Collage of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea. 2. Collage of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea. 3. College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea. 4. Department of Neurosurgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Jeollanam-do, Republic of Korea. 5. Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea. 6. Korean Lichen Research Institute, Sunchon National University, Sunchon, Republic of Korea. Electronic address: jshur1@sunchon.ac.kr. 7. Collage of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea. Electronic address: hangunkim@sunchon.ac.kr.
Abstract
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.
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.
Authors: Mücahit Varlı; Huong T Pham; Seong-Min Kim; İsa Taş; Chathurika D B Gamage; Rui Zhou; Sultan Pulat; So-Yeon Park; Nüzhet Cenk Sesal; Jae-Seoun Hur; Kyo Bin Kang; Hangun Kim Journal: Front Pharmacol Date: 2022-09-08 Impact factor: 5.988
Authors: Klaudia Petrova; Martin Kello; Tomas Kuruc; Miriam Backorova; Eva Petrovova; Maria Vilkova; Michal Goga; Dajana Rucova; Martin Backor; Jan Mojzis Journal: Biomolecules Date: 2021-03-12