PRECLINICAL REPORTSEffect of artesunate on immune cells in ret-transgenic mouse melanoma modelRamacher, Marcela; Umansky, Viktora; Efferth, ThomasbAuthor Information aGerman Cancer Research Center, Skin Cancer Unit (G300) bGerman Cancer Research Center, Pharmaceutical Biology (C015), Im Neuenheimer Feld, Heidelberg, Germany Correspondence to Thomas Efferth, PhD, Department of Pharmaceutical Biology, Institute of Pharmacy, University of Mainz, Staudingerweg 5, 55099 Mainz, Germany Tel: +49 6221 423426; e-mail: email@example.com Received 17 June 2009 Revised form accepted 14 July 2009 Anti-Cancer Drugs: November 2009 - Volume 20 - Issue 10 - p 910-917 doi: 10.1097/CAD.0b013e328330caba Buy Metrics Abstract The antimalarial artesunate also exerts profound cytotoxicity toward tumor cells. Earlier investigations controversially discussed a possible immunosuppressive function of artemsinin and its derivatives. This poses the question, whether immunosuppressive activity counteracts the anticancer activity in vivo. To clarify this issue, we used a transgenic mouse spontaneous melanoma model, in which ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. ret-transgenic mice were previously reported to accumulate melanoma-specific effector memory T cells and natural killer (NK) cells in the primary tumors and metastatic lymph nodes. In the present investigation, we monitored effects of artesunate on the CD4+ and CD8+ T cells as well as Treg and NK cells from ret-transgenic tumor-bearing mice and nontransgenic littermates in vivo. In addition, we investigated cytostatic and cytotoxic activity of artesunate on ret-tumor cells established from the mouse primary tumor. Artesunate inhibited growth of ret-tumor cells and induces their apoptosis in a concentration-dependent manner (0.1–200 μmol/l). Furthermore, we did not find considerable effects of artesunate on the immune function as measured by major cell populations of the immune system; that is, CD4+ and CD8+ T cells as well as Treg and NK cells both from ret-transgenic mice and nontransgenic C57BL/6 littermates treated for 2 weeks with a daily dose of 1 mg artesunate. These results indicate that the cytostatic and apoptotic effects of artesunate are not diminished by concomitant immunosuppression. © 2009 Lippincott Williams & Wilkins, Inc.