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Open AccessArticle

Lichen Secondary Metabolite Physciosporin Decreases the Stemness Potential of Colorectal Cancer Cells

by Yi Yang 1,2,3,†, Thanh Thi Nguyen 1,2,4,†, Iris Pereira 5, Jae-Seoun Hur 2 and Hangun Kim 1,*
1
College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea
2
Korean Lichen Research Institute, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea
3
Department of Pharmacology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea
4
Faculty of Natural Science and Technology, Tay Nguyen University, Buon Ma Thout 630000, Vietnam
5
Institute of Biological Sciences, Universidad de Talca, Talca 747-721, Chile
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(12), 797; https://doi.org/10.3390/biom9120797
Received: 27 October 2019 / Revised: 24 November 2019 / Accepted: 27 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
Secondary metabolites of lichens are promising bioresources for candidate anti-cancer drugs. Accordingly, several approaches have been proposed for screening these molecules for novel anti-cancer lead compounds. In this study, we found that a non-toxic concentration of physciosporin, a compound isolated from Pseudocyphellaria granulata, significantly decreased colony formation on soft agar and spheroid formation by CSC221 cancer stem-like cells. Physciosporin also decreased spheroid formation in other colorectal cancer cell lines, including DLD1, Caco2, and HT29. Aldehyde dehydrogenase-1 (ALDH1), the most important cancer stem marker, was sharply downregulated at both the protein and mRNA level following treatment with physciosporin. Physciosporin also decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli), as well as the Hes1 and CSL promoters, in reporter assays. Moreover, the drug significantly suppressed spheroid formation in CSC221 cells overexpressing Gli1/2 or EN1 (an S2-cleaved but membrane-tethered form of human Notch1) but did not suppress spheroid formation in cells overexpressing both Gli1/2 and ∆EN1, suggesting that physciosporin suppresses colon cancer cell stemness through the Sonic hedgehog and Notch signaling pathways. Together, these results demonstrate for the first time that physciosporin is a potent inhibitor of colorectal cancer cell stemness.
Keywords: lichen; Pseudocyphellaria granulate; secondary metabolites; physciosporin; cancer stemness inhibition; colorectal cancer cells lichen; Pseudocyphellaria granulate; secondary metabolites; physciosporin; cancer stemness inhibition; colorectal cancer cells
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MDPI and ACS Style

Yang, Y.; Nguyen, T.T.; Pereira, I.; Hur, J.-S.; Kim, H. Lichen Secondary Metabolite Physciosporin Decreases the Stemness Potential of Colorectal Cancer Cells. Biomolecules 2019, 9, 797.

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