Artemisinin Mechanism of Action Artemisinin is a chemical called a sesquiterpene lactone that contains an endoperoxide moiety (-C-O-O-C-), or internal double-oxygen bridge, which forms free radicals when exposed to free iron. Artemisinin is thought to act by a two-step mechansim. First, intracellular free iron induces a chemical reaction in the endoperoxide moiety that generates carbon-based free radicals. Second, these free radicals act as alkylating agents inducing apoptotic cell death through caspase pathway activation. This reaction is selectively toxic to cells in pathologic conditions in which intracellular free iron levels are uncontrollably elevated, such as cancer cells. By comparison, rapidly dividing normal cells are better at regulating and storing iron, and are not as affected by artemisinin's free radical mechanism, which has been confirmed in numerous studies.
Multi-Targeted, Selectively Promiscuous™ For the past several years, the biopharmaceutical industry has focused primarily on cancer drugs that target a single gene or enzyme in a pathway involved in cancer disease progression. More recent research has suggested that "promiscuous drugs", i.e., therapeutics that target multiple genes and enzymes involved in several pathways in cancer, may be more efficacious with fewer adverse side effects.
Due to intracellular iron-mediated activation, artemisinin therapeutics are highly selective to cancer and other abnormally proliferating cells. Recent studies have indicated that in addition to free radicals and ROS-induced apoptosis, artemisinin inhibits or downregulates other up/downstream molecular targets and pathways listed below, which may further explain and reinforce the therapeutic benefits and promise of artemisinin-based therapies in treating cancer and other serious proliferative and inflammatory disorders.
Inhibition or Downregulation of:
• Vascular Endothelial Growth Factor (VEGF)
• Hypoxia Inducible Factor-1 Alpha (HIF-1 alpha)
• Estrogen Receptor Alpha (ER-alpha)
• Human Epidermal Growth Factor Receptor 2 (HER2/neu)