Effects of phenoxyartemisinin derivatives on the inhibition of colorectal cancer and cancer stem cells

Abstract As the aging population grows, the incidence of colorectal cancer (CRC) is increasing, making it a significant global health concern. Despite advancements in surgical and chemotherapeutic treatments, the five‐year survival rate for CRC remains around 65%, largely due to the presence of chemotherapy‐resistant cancer stem cells (CSCs). Artemisinin derivatives, known for their antimalarial properties, have shown potential anticancer activity. This study focuses on phenoxyartemisinin compounds and their effects on colon cancer cells and CSCs. We synthesized C‐10 substituted phenoxyartemisinins and evaluated their efficacy using in vitro and in vivo models. The results demonstrated that phenoxyartemisinins, particularly compound 4a , significantly inhibited the growth of colon CSCs and reduced sphere formation, an indicator of stem cell activity. Additionally, in a mouse tumor xenograft model, 4a showed substantial tumor reduction with minimal toxicity. These findings suggest that phenoxyartemisinin compounds could offer a novel therapeutic approach for CRC, targeting both cancer cells and CSCs to potentially prevent recurrence and improve patient outcomes.