SHH is an important regulator of organogenesis during embryonic development 11. In addition, ALDH1 is a stemness marker, overexpression of which correlates with development of CSCs 9, and Musashi-1 promotes chemoresistance and cancer stemness in colorectal cancers 10. CSCs express cluster of differentiation 133 (CD133), CD44, leucine-rich repeat-containing G protein-coupled receptor-5 (Lgr-5), and ephrin type-B receptor 1 (EPHB1) 8, which are stem cell surface markers. Targeting CSCs primarily aims to block expression of stemness markers and embryonic signaling pathways (i.e., the sonic Hedgehog (SHH) and Notch pathways). ![]() Therefore, it is important to prevent colon tumor formation and to search for new therapeutics that target CSCs. Although many therapeutic agents have been developed for the treatment of colon cancer, many treatments fail 4. Colon cancer is the second largest cause of cancer-related death, and the third most common cancer in the world in all sexes 7. CSCs are found in many different types of cancer, including brain, kidney, breast, blood, lung, pancreatic, prostate, and colon cancers 5, 6. ![]() Increasing evidence shows that cancer stem cells (CSCs) contribute to chemoresistance 2, 3, which limits the efficacy of anticancer drugs 4. Consequently, an acetone extract and 1′- O-methyl-averantin isolated from EL001672 suppresses colorectal cancer stemness by regulating the sonic Hedgehog and Notch signaling pathways.Ĭancer stemness cells are known for their potential for self-renewal and their ability to initiate growth of heterogeneous cancer cells 1. The results showed that the crude extract and the 1′- O-methyl-averantin inhibited Gli1, Gli2, SMO, Bmi-1, Notch-1, Hes-1, and the CSL complex. To further characterize the mechanism underlying anti-stemness activity, we examined sonic Hedgehog and Notch signaling. Both the crude extract and 1′- O-methyl-averantin suppressed spheroid formation in CRC cell lines, and downregulated expression of stemness markers ALDH1, CD44, CD133, Lgr-5, Msi-1, and EphB1. However, 1′- O-methyl-averantin showed cytotoxic effects against cancer cell lines at 50 μg/mL and 25 μg/mL. The acetone extract of EL001672 did not affect cell viability. The anticancer activity of the extract and the isolated compound was evaluated by qRT-PCR and western blotting, and in cell viability, spheroid formation, and reporter assays. Column chromatography and reverse-phase HPLC were used to isolate an active compound. The culture broth was extracted with acetone to obtain a crude extract. EL001672 (KACC 83021BP), derived from Cetraria sp., was grown in culture medium. The endolichenic fungus Jackrogersella sp. EL001672 (derived from the lichen Cetraria sp.) and the isolated compound 1′- O-methyl-averantin to inhibit development of cancer stemness. ![]() This study examined the ability of an extract of Jackrogersella sp. New alternative therapeutics are needed to inhibit the growth of tumor stem cells. Colorectal cancer stem cells are capable of self-renewal and differentiation into cancer cells, which makes cancers difficult to eradicate. Endolichenic fungi are host organisms that live on lichens and produce a wide variety of secondary metabolites.
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