Abstract
Preclinical investigation and clinical experience have provided evidence on the potential anticancer effect of artemisinin and its derivatives (ARTs) in the recent two decades. The major mechanisms of action of ARTs may be due to toxic-free radicals generated by an endoperoxide moiety, cell cycle arrest, induction of apoptosis, and inhibition of tumor angiogenesis. It is very promising that ARTs are expected to be a new class of antitumor drugs of wide spectrum due to their detailed information regarding efficacy and safety. For developing repurposed drugs, many other characteristics of ARTs should be studied, including through further investigations on possible new pathways of anticancer effects, exploration on efficient and specific drug delivery systems-especially crossing biological barriers, and obtaining sufficient data in clinical trials. The aim of this review is to highlight these achievements and propose the potential strategies to develop ARTs as a new class of cancer therapeutic agents.
Highlights
One of every 5000–10,000 prospective anticancer agents are approved by the Food and DrugAdministration (FDA) and only 5% of oncology drugs that enter Phase I clinical trials are approved
We found that artemisinin and dihydroartemisinin exhibit significant anticancer effects against human hepatoma cells with minimal effects on normal cells, regardless of p53 status, and that the latter was effective in ovarian cancer when administered alone or in combination with carboplatin [20,21]
The former includes a large class of growth factors or cytokines such as Vascular endothelial growth factor (VEGF), Basic Fibroblast Growth Factor, angiopoietin, Matrix metalloproteinases (MMPs), interleukin-1 (IL-1), IL-8, and the latter includes endostain, angiostain, Tissue inhibitor of matrix metalloproteinases (TIMPs), etc
Summary
One of every 5000–10,000 prospective anticancer agents are approved by the Food and Drug. Administration (FDA) and only 5% of oncology drugs that enter Phase I clinical trials are approved. These failure rates underscore the need for alternative efforts for drug development. An antidiabetic drug, is a potent 50 AMP-activated protein kinase (AMPK)-independent antiproliferative agent and associated with the decreased risk of the occurrence of cancers [6,7]. A highly toxic medicine that is used to treat lung diseases and psoriasis at very low doses, showed outstanding curative effects in clinical cases with acute promyelocytic leukemia [12,13].
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