Mechanism of Fas‐mediated cell death and its enhancement by TNF‐α in human salivary gland adenocarcinoma cell line HSG

Chosa, Naoyuki; Kyakumoto, Seiko; Kito, Noriko; Kamo, Masaharu; Sato, Nobuko

doi:10.1111/j.1600-0722.2004.00145.x

Cited by 10 publications

(7 citation statements)

References 49 publications

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“…Cytokines such as TNF-alpha, IFN-gamma and FasL have previously been reported to have an anti-proliferative effect on salivary gland cells [18,23,60]. To analyze the ability of these cytokines to induce apoptosis, HSG cells were treated individually with TNF-alpha (50 g/ml), IFN-gamma (10 ng/ml), apoptosis-inducing anti-Fas antibody (50 ng/ml), or a combination of these cytokines, as indicated in the Figure Legend, for 24 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Pro-inflammatory cytokines such as TNF-alpha, IFNgamma, and Fas ligand are potent initiators of apoptosis in various cell types, including salivary gland cells. In addition, TNF-alpha, IFN-gamma, and FasL are known to be present in the focal infiltrates of SS patients and are believed to be the primary inducers of apoptotic cell death in the salivary gland cells of SS patients [14][15][16][17][18]60].…”

Section: Discussionmentioning

confidence: 99%

“…Recent work in HSG cells suggests that TNF-alpha and IFN-gamma can induce FasL expression. In addition, the induction of FasL in HSG cells triggers the initiation of the death receptor signaling pathway and caspase 8 without mitochondrial involvement [60].…”

Section: Introductionmentioning

confidence: 99%

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Interferon-gamma sensitizes the human salivary gland cell line, HSG, to tumor necrosis factor-alpha induced activation of dual apoptotic pathways

2006

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Activated immune cells secrete proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma) and Fas ligand (FasL) and these cytokines have been reported to induce apoptosis in numerous cell types. Apoptotic cell death has been associated with the progression of numerous autoimmune diseases. Proinflammatory cytokines are reportedly involved in apoptosis in the salivary glands of patients with Sjögren's syndrome (SS); an autoimmune disorder characterized by the destruction of salivary and lachrymal glands. In this study, we used the HSG cell line to determine if exposure to proinflammatory cytokines induces apoptosis in human salivary gland cells. In addition, we identified the mediators controlling the apoptotic process in response to TNF alpha and IFN gamma. TNF-alpha and IFN-gamma induced apoptosis in HSG cells and resulted in the activation of caspase 8 and the "death receptor" pathway. We further determined that caspase 9 and the "mitochondrial" pathway was also activated. Induction of the intrinsic and extrinsic pathways in HSG cells resulted in substrate cleavage by effector caspases, in particular the cleavage of alpha II spectrin, an autoantigen in Sjögren's syndrome. Our results suggest that HSG cells provide a model system to study processes regulating proinflammatory cytokine-induced apoptotic cell death.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interferon-gamma sensitizes the human salivary gland cell line, HSG, to tumor necrosis factor-alpha induced activation of dual apoptotic pathways

2006

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“…On the other hand, this combination might activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Jun-N terminal kinase (JNK) signal pathway by recruitment of TNF receptor-associated factor (TRAF2) and Receptor interacting protein (RIP) [24-26]. 1.0 mg/kg ESC-2 obviously increased TNFR1 expression which suggested that ESC-2 inducing apoptosis of NCI-H460 cells might be related to upregulation of TNFR1 receptor.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay

Liu

Yang

Zhang

et al. 2014

BMC Complement Altern Med

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BackgroundStellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo.MethodsIn this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively.ResultsThe results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment.ConclusionESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

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“…In our study, the TNF-α protein expression levels of the low-, medium-, and high-dose ASMq groups are significantly higher than those of the U27 model group and CTX group. Recent studies shows that the anti-tumor effects of TNF-α were primarily enhanced by the body’s cellular and humoral immune functions, inhibiting tumor angiogenesis and directly inducing tumor cell apoptosis [41, 42]. Serum TNF-α and IL-12 levels has been reported to be increased in tumor-bearing mice treated with astragalus polysaccharides (APS)-induced mature dendritic cell (DC) vaccine therapy, suggesting that the anti-tumor effects of this therapy could stimulates the immune cells of tumor-bearing mice to produce anti-tumor cytokines TNF-α and IL-12 [43].…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer (U27) mouse model

Omarniyaz

Yang

et al. 2016

BMC Complement Altern Med

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BackgroundAbnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. it was showed that total flavonoids of ASMq could inhibit the proliferation and enhance the antioxidant ability of human cervix cancer HeLa cell. This study attempts to confirm these effects on the transplanted cervical cancer (U27) mouse model in vivo.MethodsForty eight Kunming mice were randomly divided in to six groups: normal control group (Control group), U27 tumor model group (Model group), cyclophosphamide administration group (CTX group),low-dose ASMq group (ASMq.L group), medium-dose ASMq group (ASMq.M group), and high-dose ASMq group (ASMq.H group). The five groups except normal control group transplanted with cervical cancer (U27) cells. We observed mice tumor inhibition rate and conducted the histopathological analysisUsing the western blot assay, the expression of TGF-β1 and TNF-α protein in transplanted cervical cancer U27 tumor tissue were detected.ResultsThe tumor inhibition rates of CTX group, ASMq.L group, ASMq.M group, and ASMq.H group were 72.21, 31.27, 60.53 and 51.94% respectively, has obvious antitumor effect. ASMq significantly promote the spleen tlymphocyte proliferation of transplanted cervical cancer U27 mice. Invasive growth and diffusion rate in tumor tissue were accelerate in the transplanted cervical cancer U27 model group. Tumor tissue necrosis of tumor cells are smaller in the medium, high dosage group. Compared with the U27 model group, the expression levels of TGF-β1 protein and TNF-α protein expression exhibited statistically significant decreased in the mice tumor tissues in the CTX administration group and the ASMq administration group.ConclusionsASMq has some antitumor effects on U27 model mice in vivo, The effects are achieved not only by improving the immune function of U27 model mice, but also by inhibiting the expression levels of TGF-β1 protein while promoting the expression levels of TNF-α protein.

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Mechanism of Fas‐mediated cell death and its enhancement by TNF‐α in human salivary gland adenocarcinoma cell line HSG

Cited by 10 publications

References 49 publications

Interferon-gamma sensitizes the human salivary gland cell line, HSG, to tumor necrosis factor-alpha induced activation of dual apoptotic pathways

Interferon-gamma sensitizes the human salivary gland cell line, HSG, to tumor necrosis factor-alpha induced activation of dual apoptotic pathways

Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay

Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer (U27) mouse model

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