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

Yang Y.; Nguyen T.T.; Pereira I; Hur J.-S.; Kim H.

Abstract

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 Delta 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.

Más información

Título según WOS: Lichen Secondary Metabolite Physciosporin Decreases the Stemness Potential of Colorectal Cancer Cells
Título según SCOPUS: Lichen secondary metabolite physciosporin decreases the stemness potential of colorectal cancer cells
Título de la Revista: BIOMOLECULES
Volumen: 9
Número: 12
Editorial: MDPI
Fecha de publicación: 2019
Idioma: English
DOI:

10.3390/biom9120797

Notas: ISI, SCOPUS