title: Safrole suppresses murine myelomonocytic leukemia WEHI-3 cells in vivo, and stimulates macrophage phagocytosis and natural killer cell cytotoxicity in leukemic mice.
abstract: Many anticancer drugs are obtained from phytochemicals and natural products. However, some phytochemicals have mutagenic effects. Safrole, a component of Piper betle inflorescence, has been reported to be a carcinogen. We have previously reported that safrole induced apoptosis in human oral cancer cells in vitro and inhibited the human oral tumor xenograft growth in vivo. Until now, there is no information addressing if safrole promotes immune responses in vivo. To evaluate whether safrole modulated immune function, BALB/c mice were intraperitoneally injected with murine myelomonocytic WEHI-3 leukemia cells to establish leukemia and then were treated with or without safrole at 4 and 16 mg/kg. Animals were sacrificed after 2 weeks post-treatment with safrole for examining the immune cell populations, phagocytosis of macrophages and the natural killer (NK) cells' cytotoxicity. Results indicated that safrole increased the body weight, and decreased the weights of spleen and liver in leukemic mice. Furthermore, safrole promoted the activities of macrophages phagocytosis and NK cells' cytotoxicity in leukemic mice when compared with untreated leukemic mice. After determining the cell marker population, we found that safrole promoted the levels of CD3 (T cells), CD19 (B cells) and Mac-3 (macrophages), but it did not affect CD11b (monocytes) in leukemic mice. In conclusion, safrole altered the immune modulation and inhibited the leukemia WEHI-3 cells in vivo.
authors.affiliation: Department of Dental Hygiene, China Medical University, Taichung 404, Taiwan.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Chun-Shu
authors.initials: CS
authors.lastname: Yu
authors.forename: Jo-Hua
authors.initials: JH
authors.lastname: Chiang
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Hsiung-Kwang
authors.initials: HK
authors.lastname: Chung
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Heng-Chien
authors.initials: HC
authors.lastname: Ho
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000097:blood; D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D039481:CD11b Antigen / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010587:Phagocytosis / Q000187:drug effects; D012451:Safrole / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D039481:CD11b Antigen; D017252:CD3 Complex; D012451:Safrole
keywords: NK cell cytotoxicity; leukemic mice; macrophage phagocytosis; murine leukemia WEHI-3 cells; safrole