title: TNF-α produced by SEC2 mutant (SAM-3)-activated human T cells induces apoptosis of HepG2 cells.
abstract: Staphylococcal enterotoxins C2 (SEC2) is a classical model of superantigens (SAg), which has the powerful ability to activate T cells as well as induce massive cytokine production. This property makes SEC2 and its mutants well concerned as a potential new immune-regulatory agent for cancer therapy. We previously constructed a SEC2 mutant named SAM-3, which had prominently antitumor activity in BALB/c mice model. But, the underlying molecular mechanism for stimulation of human peripheral blood mononuclear cells (PBMCs) and antitumor effect on human tumor cells induced by SAM-3 is not clear. Here, we showed that SAM-3 could activate human TCR Vβ 12, 13A, 14, 15, 17, and 20 CD8(+) subgroup T cells, which secreted the cytokines IL-2, IFN-γ, and TNF-α, and exhibit stimulation activity in a dose-dependent manner. TNF-α secreted from activated T cells could induce apoptosis and G1-phase arrest and lead to the antitumor effect in HepG2 cells. Meanwhile, SAM-3 upregulated the expression of tumor necrosis factor receptor 1 (TNFR1) mRNA and activity of caspase-3 and caspase-8. We also found that the antitumor activity and activity of caspase-3 and caspase-8 were decreased when the neutralizing TNF-α monoclonal antibody presented. These data suggest that TNF-α secreted by SAM-3-activated T cells is an important factor in inducing apoptosis in HepG2 cells.
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China.
authors.forename: Mingkai
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Song
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China.
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Su
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China. hwzhang@iae.ac.cn.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Applied Ecology, Chinese Academy of Sciences, No.72 Wenhua Road Shenhe Dis., Shenyang, Liaoning, 110016, People's Republic of China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004768:Enterotoxins; D050505:Mutant Proteins; D014409:Tumor Necrosis Factor-alpha; C034959:enterotoxin C, staphylococcal
keywords: Antitumor; Apoptosis; Staphylococcal enterotoxin C2; Superantigen; TNF-α