Lobaric acid suppresses the stemness potential of colorectal cancer cells through mTOR/AKT.

Stereocaulon alpinum has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from Stereocaulon alpinum against the stemness potential of CRC cells and investigated the possible underlying mechanisms. The results demonstrated that LA did not inhibit the cell viability of CSC221 and DLD1. In addition, LA significantly decreased the spheroid formation of CSC221 and DLD1. Moreover, LA treatment suppressed cancer stem cell (CSC) markers; aldehyde dehydrogenase 1 (ALDH1), B-cell-specific Moloney leukemia virus insertion site 1 (BMI1), musashi1 (MSI1), and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), along with the sonic hedgehog (Shh) and mTOR/AKT pathways that contribute significantly to maintaining the stemness of CRC cells. Therefore, LA may be a new therapeutic approach for reducing the stemness of CRC cells.