Arteether exerts antitumor activity and reduces CD4+CD25+FOXP3+ T-reg cells in vivo

Iran J Immunol. 2013 Sep;10(3):139-49.

Abstract

Background: Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells.

Objective: To investigate the cytotoxic and immunomodulatory properties of Arteether in-vivo and in-vitro.

Methods: In this study, we used MTT assay for evaluation of cytotoxicity of Arteether on tumor cell line and Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals. Balb/c mice were subcutaneously transplanted with tumor tissue taken from Spontaneous Mouse Mammary Tumor (SMMT) bearing female mice. Arteether was administered to breast tumor-bearing Balb/c mice at a dose of 6mg/kg/day intraperitoneally. Tumor sizes, lymphocyte proliferation, cytokines production, and the percentage of splenic T-reg cells were measured.

Results: We observed that ARE could reduce the cell growth of 4T1 cell line in a dose-dependent manner but it had no cytotoxic effect on the growth of peripheral blood lymphocytes. ARE administered intraperitoneally to tumor-bearing Balb/c mice could reduce the tumor growth rate and splenic T-reg cells. No difference in the IFN-γ, IL-10 and IL-4 production was observed between tumor antigen-stimulated splenocytes of mice treated with ARE and control mice.

Conclusion: These results underscore antitumor properties of Arteether that may aid in development of more effective antitumor agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Artemisia annua / chemistry
  • Artemisinins / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Phytotherapy*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Cytokines
  • artemotil