Artemisinin and Its Derivatives as a Repurposing Anticancer Agent: What Else Do We Need to Do?

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.

Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action

“…One prevailing hypothesis proposes free ferrous iron (Fe 2+ ) as the principal activator of artemisinin . This is an attractive viewpoint due to several reasons.…”

“…Apart from cell death, artemisinin is known to affect multiple hallmarks of cancer by inducing cell cycle arrest, inhibiting angiogenesis and impeding cancer metastasis and invasion . Much of the evidence and mechanisms behind these processes and the identities of the signaling pathways involved have been comprehensively reviewed and will not be repeated here . Instead, we will first highlight some recent studies in the use of emerging proteomics techniques to explore the complexities behind the anticancer effects of artemisinin.…”

“…Artemisinin has been linked to a wide range of cellular targets and pathways in cancer, with commonly reported representatives including the p38‐MAPK, PI3K/Akt, Ras, NF‐κB, and Wnt/β‐catenin pathways, among others, which have been reviewed comprehensively in previous publications . Considering its general mechanism of protein alkylation and the range of reported effects, it is reasonable to suggest that artemisinin functions in a promiscuous or multitarget manner rather than acting on specific cellular targets.…”

“…These include antiviral and fungicidal properties, therapeutic functions in nonmalaria parasitic diseases, anti‐inflammatory and anti‐asthma effects as well as potential anticancer functions . Considering its status as an established and well‐tolerated drug, it is naturally of interest to explore the repurposing of artemisinin for the treatment of nonparasitic diseases …”

“…It is now understood that artemisinin and its derivatives exhibit highly selective and marked cytotoxicity against a range of cancer cell types both in vitro and in vivo, and great strides have been taken to unravel the mechanisms behind these effects . These studies have been covered by a good number of excellent reviews . The recent years have seen a surge in interest for artemisinin following the awarding of the Nobel Prize for Tu's discovery and efforts .…”