title: Biological activities of novel recombinant tumor necrosis factor having N-terminal amino acid sequences derived from cytotoxic factors produced by THP-1 cells.
abstract: Eight species of novel recombinant tumor necrosis factor-S (rTNF-SAM group) were constructed in which N-terminal amino acid sequences were based on that of TNF-S from THP-1 cells with higher basicity than conventional rTNF-alpha. Two of this rTNF-SAM group, denoted as rTNF-SAM1 and rTNF-SAM2, showed more cytocidal activity on A549 lung carcinoma cells and G401 Wilm's tumor cells than did rTNF-alpha. In addition to these cell lines, rTNF-SAM1 revealed strong cytocidal activity on T24 bladder carcinoma cells, which are resistant to rTNF-alpha. Moreover, possible cachectin activity of rTNF-SAM2 seemed to be lower than that of conventional rTNF-alpha, suggesting that rTNF-SAM2 has less side effects. Actually, toxicity as expressed by LD50 value of rTNF-SAM2 as well as others of the rTNF-SAM group was significantly lower than that of conventional rTNF-alpha. Thus, newly constructed rTNF-SAM1 and rTNF-SAM2 should be more promising antitumor reagents for clinical use, since they were shown to be superior to conventional rTNF-alpha both in antitumor effect and in less side effects.
authors.affiliation: Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Soma
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: N
authors.initials: N
authors.lastname: Kitahara-Tanabe
authors.forename: T
authors.initials: T
authors.lastname: Gatanaga
authors.forename: H
authors.initials: H
authors.lastname: Inagawa
authors.forename: M
authors.initials: M
authors.lastname: Kawakami
authors.forename: D
authors.initials: D
authors.lastname: Mizuno
mesh_terms: D000595:Amino Acid Sequence; D008066:Lipolysis / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D009396:Wilms Tumor / Q000188:drug therapy*
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase