Abstract
Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.
Highlights
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide [1], and its high mortality rate has made it a priority in clinical cancer therapy [2]
No attempt has been made to screen anti-cancer activity based on cancer stem cells (CSCs)-like work, we examined the inhibitory activity of 11 lichen species from Chile against the stemness traits, which has the potential to identify more efficient chemotherapeutic agents
In the potential of colorectal cancer (CRC) cells, and investigated the possible molecular mechanisms underlying this present work, we examined the inhibitory activity of 11 lichen species from Chile against the stemness inhibitory activity to identify novel compounds that could lower the chemoresistance of target potential of CRC cells, and investigated the possible molecular mechanisms underlying this inhibitory therapeutic drugs
Summary
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide [1], and its high mortality rate has made it a priority in clinical cancer therapy [2]. Resistance to chemotherapy occurs in 90% of patients with metastatic cancer, and this is believed to be the main reason for treatment failure, despite the development of numerous therapeutic agents targeting CRC in the past decade [4]. Mounting evidence indicates that cancer stem cells (CSCs) contribute to chemotherapy resistance [5,6,7], and recent studies suggest that the efficiency of chemotherapy could be improved by exploiting the therapeutic opportunities provided by the molecular properties of CSCs. Cluster of differentiation (CD) 133 [8,9], CD44 [10], and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) [11] are colorectal CSC markers related to Molecules 2018, 23, 2968; doi:10.3390/molecules23112968 www.mdpi.com/journal/molecules.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
