Artemisia annua L. is used throughout Asia and Africa as
tea and press juice to treat
malaria and related symptomes (
fever,
chills). Its active ingredient,
artemisinin (ARS), has been developed as
antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to
malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against
tumors. The cellular response of ARS and its derivatives (
dihydroartemisinin,
artesunate,
artemether,
arteether) towards
cancer cells include oxidative stress response by
reactive oxygen species and
nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis,
necrosis, necroptosis, oncosis), inhibition of angiogenesis and
tumor-related signal transduction pathways (e.g. Wnt/β-
catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.