Biomolecules
Biomolecules
4 years ago

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

Lichen Secondary Metabolite Physciosporin Decreases the Stemness Potential of Colorectal Cancer Cells
Yang, Nguyen, Pereira, Hur, Kim
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.

Publisher URL: https://www.mdpi.com/2218-273X/9/12/797

Open URL: https://www.mdpi.com/2218-273X/9/12/797/pdf

DOI: 10.3390/biom9120797

Open access
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