An Endolichenic Fungi-Derived Fatty Acid, cis-10-Nonadecenoic acid, Suppresses Colorectal Cancer Stemness

Abstract

Endolichenic fungi (ELF), symbionts of lichens, have been reported to produce diverse bioactive secondary metabolites with promising pharmaceutical potential. In this study, we isolated and identified an ELF, EL001668 (KACC 83020BP), from Cetraria laevigata Rass., and assessed its crude extract and bioactive compounds against colorectal cancer (CRC) stem cell activity. cis-10-nonadecenoic acid (c-NDA), isolated through bioactivity-guided fractionation exerted substantial inhibitory effects on CRC stemness, such as the suppression of spheroid formation and the downregulation of the key stem cell markers ALDH1, CD44, and CD133. Comparative analysis with the omega-3 fatty acids EPA and DHA, with well-established properties, showed that c-NDA exerted comparable or superior inhibitory effects against the markers and phenotypic traits of stemness. Besides, the crude extract of EL001668 exhibited greater suppression of certain markers in comparison to the individual compounds. These findings suggest that c-NDA, in conjunction with ELF-derived compounds, holds potential as a novel therapeutic candidate targeting CRC stem cells. Taken together, the current study demonstrated that c-NDA, similar to EPA and DHA, may possess adjunct or complementary effects in cancer treatment and other diseases.