Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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Autophagy is an intracellular degradation pathway conserved in eukaryotes. ANXA6 (annexin A6) belongs to a family of calcium-dependent membrane and phospholipid binding proteins. Here, we identify ANXA6 as a newly synthesized protein in starvation-induced autophagy and validate it as a novel autophagy modulator that regulates autophagosome formation. ANXA6 knockdown attenuates starvation-induced autophagy and restoration of its expression enhances autophagy. GO (gene ontology) analysis of ANXA6 targets showed that ANXA6 interacts with many RAB GTPases and targets endocytic and phagocytosis pathways, indicating that ANXA6 exert its function through protein trafficking. ATG9A (autophagy related 9A) is the sole multi-spanning transmembrane protein and its trafficking through the recycling endosomes is an essential step for autophagosome formation. Our results showed that under starvation condition, ANXA6 enables appropriate ATG9A trafficking from endosomes to autophagosomes through RAB proteins or F-actin. In addition, restoration of ANXA6 expression suppresses mTOR (mammalian target of rapamycin) activity through the inhibition of the PI3K (phosphoinositide 3-kinase)-AKT and the ERK (extracellular signal-regulated kinase) signaling pathway, which is a

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