Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside.

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Planta Med. 2007 Apr;73(4):299-309. Epub 2007 Mar 12.

Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin--from bench to bedside.
Efferth T.
German Cancer Research Center, Heidelberg, Germany.

metabolites from plants serve as defense against herbivores, microbes,
viruses, or competing plants. Many medicinal plants have
pharmacological activities and may, thus, be a source for novel
treatment strategies. During the past 10 years, we have systematically
analyzed medicinal plants used in traditional Chinese medicine and
focused our interest on Artemisia annua L. (qinhao, sweet wormwood). We
found that the active principle of Artemisia annua L., artemisinin,
exerts not only antimalarial activity but also profound cytotoxicity
against tumor cells. The inhibitory activity of artemisinin and its
derivatives towards cancer cells is in the nano- to micromolar range.
Candidate genes that may contribute to the sensitivity and resistance
of tumor cells to artemisinins were identified by pharmacogenomic and
molecular pharmacological approaches. Target validation was performed
using cell lines transfected with candidate genes or corresponding
knockout cells. The identified genes are from classes with diverse
biological functions; for example, regulation of proliferation (BUB3,
cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and
its receptor, matrix metalloproteinase-9, angiostatin,
thrombospondin-1) or apoptosis (BCL-2, BAX, NF-kappaB). Artesunate
triggers apoptosis both by p53-dependent and -independent pathways.
Antioxidant stress genes (thioredoxin, catalase, gamma-glutamylcysteine
synthetase, glutathione S-transferases) as well as the epidermal growth
factor receptor confer resistance to artesunate. Cell lines
overexpressing genes that confer resistance to established antitumor
drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide
reductase) were not cross-resistant to artesunate, indicating that
artesunate is not involved in multidrug resistance. The anticancer
activity of artesunate has also been shown in human xenograft tumors in
mice. First encouraging experience in the clinical treatment of
patients suffering from uveal melanoma calls for comprehensive clinical
trials with artesunate for cancer treatment in the near future.