title: Anti-tumor and immunomodulatory activity of iron hepta-tungsten phosphate oxygen clusters complex.
abstract: Polyoxometalates (POMs) have attracted a considerable attention due to their unique structural characteristics, physicochemical properties and biological activities. In this study, iron hepta-tungsten phosphate oxygen clusters complex Na12H[Fe(HPW7O28)2]·44H2O (IHTPO) was synthesized and evaluated for in vitro cytotoxic activities on human hepatoma HepG2, leukemia K562, lung carcinoma A549, and large cell lung cancer NCI-H460 cells, therapeutic efficacies on mice transplantable tumor, and immunomodulatory potentials on the immune response in tumor-bearing mice. IHTPO exhibited lower in vitro cytotoxic activities against four human tumor cell lines, with the IC50 values being higher than 62.5μM (ca. 300μg/ml). IHTPO, however, significantly inhibited the growth of S180 sarcoma transplanted in mice. It was further showed that IHTPO could not only significantly promote splenocytes proliferation, NK cell and CTL activity from splenocytes, but remarkably enhance serum antigen-specific IgG, IgG2a and IgG2b antibody levels in S180-bearing mice. IHTPO also significantly promoted Th1 cytokines IFN-γ and IL-2 production, and up-regulated the mRNA expression levels of IFN-γ, IL-2 and Th1 transcription factors T-bet and STAT-4 in splenocytes from the S180-bearing mice. These results suggested that IHTPO significantly inhibited the growth of mice transplantable tumor, and that its in vivo antitumor activity might be achieved by improving Th1 protective cell-mediated immunity. IHTPO could act as antitumor agent with immunomodulatory activity.
authors.affiliation: Institute of Materia Medica, College of Pharmaceutics and Material Engineering, Jinhua Polytechnic, Jinhua 321000, China. Electronic address: zbs_ky@163.com.
authors.forename: Bisong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica, College of Pharmaceutics and Material Engineering, Jinhua Polytechnic, Jinhua 321000, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Institute of Materia Medica, College of Pharmaceutics and Material Engineering, Jinhua Polytechnic, Jinhua 321000, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Materia Medica, College of Pharmaceutics and Material Engineering, Jinhua Polytechnic, Jinhua 321000, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, College of Pharmaceutics and Material Engineering, Jinhua Polytechnic, Jinhua 321000, China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007155:Immunologic Factors / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D058085:Iron Compounds / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D012510:Sarcoma 180 / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014414:Tungsten / Q000494:pharmacology*; D017973:Tungsten Compounds / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D058085:Iron Compounds; D017973:Tungsten Compounds; D007501:Iron; D010100:Oxygen; D014414:Tungsten
keywords: Antitumor; Immunomodulatory; Iron hepta-tungsten phosphate oxygen clusters complex (IHTPO); Polyoxometalates (POMs); Th1 immune responses