Effect of artesunate on immune cells in ret-transgenic mouse melanoma model.

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 micromol/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.

• Authors: Marcel Ramacher, Viktor Umansky, Thomas Efferth
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 20 Issue 10 Pg. 910-7 (Nov 2009) ISSN: 1473-5741 [Electronic] England
• PMID: 19745721 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Artemisinins
• Artesunate
• Proto-Oncogene Proteins c-ret
• Ret protein, mouse

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Artemisinins (pharmacology, therapeutic use)
• Artesunate
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• CD8-Positive T-Lymphocytes (drug effects, immunology)
• Cell Line, Tumor
• Killer Cells, Natural (drug effects)
• Melanoma, Experimental (drug therapy, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Proto-Oncogene Proteins c-ret (genetics)
• Skin Neoplasms (drug therapy, immunology)
• T-Lymphocytes, Regulatory (drug effects)