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

İsa Taş; Jin Han; So-Yeon Park; Yi Yang; Rui Zhou; Chathurika D B Gamage; Tru Van Nguyen; Ji-Yoon Lee; Yong Jae Choi; Young Hyun Yu; Kyung-Sub Moon; Kyung Keun Kim; Hyung-Ho Ha; Sang Kyum Kim; Jae-Seoun Hur; Hangun Kim

doi:10.1016/j.phymed.2018.09.219

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

İsa Taş, Jin Han, So-Yeon Park, Yi Yang, Rui Zhou, Chathurika D B Gamage, Tru Van Nguyen, Ji-Yoon Lee, Yong Jae Choi, Young Hyun Yu, Kyung-Sub Moon, Kyung Keun Kim, Hyung-Ho Ha, Sang Kyum Kim, Jae-Seoun Hur, Hangun Kim

Sunchon National University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	10-20
Journal	Phytomedicine
Volume	56
DOIs	https://doi.org/10.1016/j.phymed.2018.09.219
Publication status	Published - 2019 Mar 15
Externally published	Yes

Free keywords

Animals
Antineoplastic Agents/administration & dosage
Apoptosis/drug effects
Cell Line, Tumor
Cell Movement/drug effects
Cell Proliferation/drug effects
Cell Survival/drug effects
Cell Transformation, Neoplastic/genetics
Colorectal Neoplasms/drug therapy
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Epithelial-Mesenchymal Transition/drug effects
Gene Expression Regulation, Neoplastic/drug effects
Humans
Lichens/chemistry
Male
Mice, Inbred BALB C
Oxepins/administration & dosage
Xenograft Model Antitumor Assays
beta Catenin/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.phymed.2018.09.219

Cite this

Taş, İ., Han, J., Park, S.-Y., Yang, Y., Zhou, R., Gamage, C. D. B., Van Nguyen, T., Lee, J.-Y., Choi, Y. J., Yu, Y. H., Moon, K.-S., Kim, K. K., Ha, H.-H., Kim, S. K., Hur, J.-S., & Kim, H. (2019). Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells. Phytomedicine, 56, 10-20. https://doi.org/10.1016/j.phymed.2018.09.219

@article{8d48aae00b4245a092d7bad32d745408,

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

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.",

keywords = "Animals, Antineoplastic Agents/administration & dosage, Apoptosis/drug effects, Cell Line, Tumor, Cell Movement/drug effects, Cell Proliferation/drug effects, Cell Survival/drug effects, Cell Transformation, Neoplastic/genetics, Colorectal Neoplasms/drug therapy, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Epithelial-Mesenchymal Transition/drug effects, Gene Expression Regulation, Neoplastic/drug effects, Humans, Lichens/chemistry, Male, Mice, Inbred BALB C, Oxepins/administration & dosage, Xenograft Model Antitumor Assays, beta Catenin/genetics",

author = "İsa Ta{\c s} and Jin Han and So-Yeon Park and Yi Yang and Rui Zhou and Gamage, {Chathurika D B} and {Van Nguyen}, Tru and Ji-Yoon Lee and Choi, {Yong Jae} and Yu, {Young Hyun} and Kyung-Sub Moon and Kim, {Kyung Keun} and Hyung-Ho Ha and Kim, {Sang Kyum} and Jae-Seoun Hur and Hangun Kim",

year = "2019",

month = mar,

day = "15",

doi = "10.1016/j.phymed.2018.09.219",

language = "English",

volume = "56",

pages = "10--20",

journal = "Phytomedicine",

issn = "0944-7113",

publisher = "Elsevier",

}

TY - JOUR

T1 - Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells

AU - Taş, İsa

AU - Han, Jin

AU - Park, So-Yeon

AU - Yang, Yi

AU - Zhou, Rui

AU - Gamage, Chathurika D B

AU - Van Nguyen, Tru

AU - Lee, Ji-Yoon

AU - Choi, Yong Jae

AU - Yu, Young Hyun

AU - Moon, Kyung-Sub

AU - Kim, Kyung Keun

AU - Ha, Hyung-Ho

AU - Kim, Sang Kyum

AU - Hur, Jae-Seoun

AU - Kim, Hangun

PY - 2019/3/15

Y1 - 2019/3/15

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents/administration & dosage

KW - Apoptosis/drug effects

KW - Cell Line, Tumor

KW - Cell Movement/drug effects

KW - Cell Proliferation/drug effects

KW - Cell Survival/drug effects

KW - Cell Transformation, Neoplastic/genetics

KW - Colorectal Neoplasms/drug therapy

KW - Dose-Response Relationship, Drug

KW - Drug Screening Assays, Antitumor

KW - Epithelial-Mesenchymal Transition/drug effects

KW - Gene Expression Regulation, Neoplastic/drug effects

KW - Humans

KW - Lichens/chemistry

KW - Male

KW - Mice, Inbred BALB C

KW - Oxepins/administration & dosage

KW - Xenograft Model Antitumor Assays

KW - beta Catenin/genetics

U2 - 10.1016/j.phymed.2018.09.219

DO - 10.1016/j.phymed.2018.09.219

M3 - Article

C2 - 30668330

SN - 0944-7113

VL - 56

SP - 10

EP - 20

JO - Phytomedicine

JF - Phytomedicine

ER -

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

Abstract

Free keywords

UN SDGs

Access to Document

Fingerprint

Cite this