Lichen Secondary Metabolite Physciosporin Decreases the Stemness Potential of Colorectal Cancer Cells
Authors: Jae-Seoun Hur
Thanh Thi Nguyen
Hangun Kim
Yi Yang
Iris Pereira
Journal: Biomolecules (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Pseudocyphellaria granulate; cancer stemness inhibition; colorectal cancer cells; lichen; physciosporin
Affiliations: College of Pharmacy, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea., Korean Lichen Research Institute, Sunchon National University, 255 Jungang-ro, Sunchon, Jeonnam 57922, Korea., Department of Pharmacology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea., Faculty of Natural Science and Technology, Tay Nguyen University, Buon Ma Thout 630000, Vietnam., Institute of Biological Sciences, Universidad de Talca, Talca 747-721, Chile.

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 ÔÅÑEN1 (an S2-cleaved but membrane-tethered form of human Notch1) but did not suppress spheroid formation in cells overexpressing both Gli1/2 and ‚àÜEN1, 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. 

Retracted: No

PubPeer comments:
 Figure 1D appears to have some overlapping images. *** Closeup  , 
 Figure 5A also. *** Closeup  , 
 Thank you for let me informed about the problem in this publication. Now, the first authors have been returned to their home country, and I tried to contact with them for this issue. I will make response as soon as possible. , 
 Thank you for informing us about the problems with the picture of Fig 1D and 5A in our publication. It is clear that we made an unintentional mistake during the data presentation. We apologize for such an error that should not being made. However, we are sure that this error does not affect the conclusion of this study. Weu2019ll contact the Editorial office to correct this and post the decision as soon as possible. Thank you for your comment.   , 
 #4 Thank you for your reply and for your intent on correcting the paper. Given the extent of issues identified above in this paper, can the authors share how it is that the errors occurred and why they are sure there is no impact on the conclusions? In addition, has the last author examined the raw data for all of the figures in this paper? I ask because I have identified multiple papers with similar issues on papers co-authored by the last author and I have not yet made an exhaustive study. ,