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Figure 2: Postulated anticancer mechanisms of action of artemisinins. (a) It has been postulated that bioactivation of artemisinin occurs in the endosome after pH-induced release of iron from internalized transferrin. Iron activated-artemisinin generates carbon-centered radicals which may mediate lysosomal disruption and generation of ROS resulting in mitochondrial damage, activation of caspases, and cell death. (b) Alternatively, it has been suggested that only specific activation of artemisinin by heme or heme-bound protein generates cytotoxic- carbon-centered radicals. In the mitochondrion, these adducts interfere with the electron transfer chain (ETC) by interacting with heme or heme-bound proteins leading to generation of ROS and apoptosis. (c) ROS harboring may induce ER stress and (d) genotoxicity.