title: Antitumor and immunomodulatory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo.
abstract: BACKGROUND
  Development of agents that specifically kill cancer cells and simultaneously elicit antitumor immune response is a step forward in cancer therapy. In the present study, we investigated whether the administration of artemether contributes to the augmentation of antitumor immunity and the regression of tumor tissues in a mouse model of breast cancer.
  
  
  METHODS
  An optimal immunostimulatory dose of artemether (ART) was defined by DTH reaction and antibody production in sRBC-challenged mice. Subsequent experiments were carried out on tumor-bearing BALB/c mice. In the first group of tumor-bearing mice, the dose of 10 mg/kg/day of artemether were intraperitoneally administered to each animal for six times. The second group was treated with 20 mg/kg/day of cyclophosphamide as a positive control, and the last group (negative control) received the ART diluents. Tumor size was measured during the 10-day experiment; on the last day, mice were sacrificed and their splenocytes and tumor infiltrating lymphocytes were harvested. The concentration of IL-4 and IFN-γ cytokines (using ELISA assay) and the percentage of splenic and tumor Treg cells (using Flowcytometry analysis) were measured.
  
  
  RESULTS
  Artemether could increase both DTH reaction and the production of hemagglutinating antibody in normal mice. Administration of ART profoundly suppressed the progression of tumor tissues. As well, it was significantly effective in the depletion of splenic CD4+ CD25+ Foxp3+ Treg cells (p-value>0.05). ART also increased the production of IL-4 (p-value<0.05) and IFN-γ (p-value>0.05). As a conclusion, the cytotoxic and immunomodulatory properties of artemether were acknowledged in vivo.
authors.affiliation: Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Vida
authors.initials: V
authors.lastname: Farsam
authors.forename: Zuhair Muhammad
authors.initials: ZM
authors.lastname: Hassan
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zavaran-Hosseini
authors.forename: Shokoofe
authors.initials: S
authors.lastname: Noori
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mahdavi
authors.forename: Moslem
authors.initials: M
authors.lastname: Ranjbar
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D037621:Artemisinins; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000077549:Artemether