• Journal of Ginseng Research
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• v.35 no.3
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• pp.294-300
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• 2011

Zearalenone (ZEA) is a phenolic resorcylic acid lactone compound produced by several species of Fusarium. ZEA has toxic effects in the testes of domestic and laboratory animals. Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has multiple pharmacological effects such as vasorelaxation, anti-thrombosis, anti-hypertension, etc. In this study, we investigated the effects of KRG extract on testicular toxicity induced by ZEA. Rats were treated with 300 mg/kg oral doses of KRG for 4 weeks every other day. The rats were then treated with a single dose of 5 mg/kg ZEA delivered intraperitoneally, whereas control rats received only doses of the vehicle. As a result, germ cell apoptosis induced by ZEA was decreased by KRG pre-treatment. In addition, Fas and Fas-L expression was reduced in rats that received KRG pre-treatment compared to ones treated with ZEA alone. In conclusion, impaired spermatogenesis resulting from ZEA treatment was prevented by KRG through Fas-Fas L modulating.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.67-79
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• 2000

Objective : Hedyotis diffusa has been used as an anticancer agent for several decades in oriental medicine. We test whether the methanol extract of the herb affects transcriptional activation factors including $NF-{\kappa}B$ and AP-1. Methods : 1. HL-60 cells were treated with various concentrations(from 200 to $50{\mu}g/ml$) of methanol extract and $H_2O$ extract($200{\mu}g/ml$)of hedyotis diffusa, After 48h later, the cells were tested for viability by MTT assay. 2. The HL-60 cells were treated with $200{\mu}g/ml$ of methanol extract for the indicated periods. First. Nuclear extracts were isolated and incubated with oligonucleotide probe of $NF-{\kappa}B$ and AP-1. Second. Nuclear extracts were isolated and reacted with p50, p65. c-rel pan-Jun, c-Jun, JunB. JunD antibody on ice for 30min. Finally The cell lysates were prepared and analyzed by western blotting using anti-Fas, anti-FasL and anti-p53 antibody. Results : 1. The methanol extract decreases the viability of human lymphoid origin leukemia HL-60 cells in a dose-dependent manner. 2. $NF-{\kappa}B$ is rapidly activated by the addition of the methanol extract, reaches a peak at 30min and gradually returns to resting level. We confirm that $NF-{\kappa}B$ is a heterodimer mainly composed of p65 subunit with c-Rel. 3. Transcriptional activation of AP-1 is detected at 30min and reaches a maximum at 1hr after stimulation of the cells with the methanol extract. AP-1 is mainly composed with Jur-D and partially Jug-B proteins. 4. the methanol extract of Hedyotis diffusa induces the expression of Fas, Fas ligand and p53 proteins of HL-60 cells in a time dependent fashion. Conclusions : These results suggest that the methanol extract of Hedyotis diffusa exerts anticancer effects to induce the death of human leukomic HL-60 cells via activation of trascriptional factors such as $NF-{\kappa}B$ and AP-1, increase in expression of Fas mediated signalling proteins, and induction of tumor suppressor gene. p53.

• Journal of Life Science
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• v.22 no.6
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• pp.815-822
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.135.2-135.2
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• 2003

Plasma membrane blebs are observed in many types of apoptotic cells, but their processes of formation remain to be clarified. In the present study, we investigated whether there is a relationship between change of intracellular phosphotyrosine levels and biochemical apoptotic events in Jurkat T cells undergoing apoptosis by agonistic anti-Fas antibody. When Jurkat cells were treated with Fas-antibody in the presence or absence of pretreatment with sodium orthovanadate ($Na_3${VO}_4$), a phosphotyrosine phosphatase (PTPase) inhibitor, membrane blebs disappeared in orthovanadate-treated cells. (omitted)

• Development and Reproduction
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• v.20 no.4
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• pp.315-329
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• 2016

Fas ligand (FasL) and its receptor Fas have been implicated in granulosa cell apoptosis during follicular atresia. Although interferon-gamma (IFN-${\gamma}$) is believed to be involved in the regulation Fas expression in differentiated granulosa or granulosa-luteal cells, the expression of this cytokine and its role in the regulation of the granulosa cell Fas/FasL system and apoptosis during follicular maturation have not been thoroughly investigated. In the present study, we have examined the presence of IFN-${\gamma}$ in ovarian follicles at different stage of development by immunohistochemistry and related their relative intensities with follicular expression of Fas and FasL, and with differences in granulosa cell sensitivity to Fas activation by exogenous agonistic Anti-Fas monoclonal antibody (Fas mAb). Although IFN-${\gamma}$ immunostaining was detectable in oocyte and granulosa cells in antral follicles, most intense immunoreactivity for the cytokine was observed in these cells of preantral follicles. Intense immunoreactivity for IFN-${\gamma}$ was most evident in granulosa cells of atretic early antral follicles where increased Fas and FasL expression and apoptosis were also observed. Whereas low concentrations of IFN-${\gamma}$ (10-100 U/mL) significantly increased Fas expression in undifferentiated granulosa cells (from preantral or very early antral follicles) in vitro, very higher concentrations (${\geq}1,000U/mL$) were required to up-regulate of Fas in differentiated cells isolated from eCG-primed (antral) follicles. Addition of agonistic Fas mAb to cultures of granulosa cells at the two stages of differentiation and pretreated with IFN-${\gamma}$ (100 U/mL) elicited morphological and biochemical apoptotic features which were more prominent in cells not previously exposed to the gonadotropin in vivo. These findings suggested that IFN-${\gamma}$ is an important physiologic intra-ovarian regulator of follicular atresia and plays a pivotal role in regulation of expression of Fas receptor and subsequent apoptotic response in undifferentiated (or poorly differentiated) granulosa cells at an early (penultimate) stage of follicular development.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2613-2618
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• 2014

Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that $Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, $CD8^+T$ cells and $Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in $CD8^+T$ lymphocytes and $Foxp3^+T$ cells in patients with HCC. Methods: $CD8^+T$ cells and $CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in $CD8^+T$ cells and FasL in $CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in $CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of $CD8^+T$ cells binding annexin V and Fas expression in $CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic $CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with $CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of $CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in $Fas^+CD8^+T$ cells in vitro are required.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1293-1298
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• 2008

The purpose of this study is to investigate the effect of a mixture of fermented Artemisiae Argi Folium and fermented Sophorae Radix (FAS) on hydrogen peroxide production within mouse macrophage Raw 264.7 with ethanol (EtOH) and nicotine. Artemisiae Argi Folium is known to have the antibacterial, immune-enhancing properties. And Sophorae Radix is also known to have the antibacterial, anti-inflammatory, anti-allergic properties. EtOH and nicotine are the ones of toxicants which could impair immunocytes like macrophage. EtOH and nicotine reduce the intracellular production of hydrogen peroxide ($H_2O_2$) of Raw 264.7. FAS increased the production of hydrogen peroxide reduced by EtOH and nicotine within Raw 264.7. These results indicate that FAS could restore the immuno-activity of macrophage impaired by EtOH and nicotine.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.5
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• pp.282-287
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• 2019

In this study, we investigated the anti-obesity effects of various mixtures of Atractylodes macrocephala (AM) and Amomum villosum (AV) water extracts on high-fat diet (HFD) induced mouse model. We classified five groups as follows; control, HFD, HFD + AM extracts : AV extracts (100mg/kg) (1:1), HFD + AM extracts : AV extracts (100mg/kg) (2:1), HFD + AM extracts : AV extracts (100mg/kg) (3:1). Oral administration of various mixtures of AM and AV extracts for 6 weeks inhibited HFD-induced increases of body, liver and epididymal fat weights. Also, lipid profiles including LDL cholesterol were improved by various mixtures of AM and AV extracts treatment compared with HFD-fed group. Lipogenesis-related genes such as acetyl coA carboxylase (ACC) and fatty acid synthase (FAS) in liver changed in a favorable way for lipid biosynthesis by HFD compared to control, but various mixtures of AM and AV extracts-treated groups did not. Our results show that various mixtures of AM and AV extracts can prevent HFD-induced obesity in mice and suggests that the mechanisms are involved in expressions and modifications of lipogenesis-related genes such as ACC and FAS in liver.

• Journal of Microbiology and Biotechnology
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• v.24 no.10
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• pp.1438-1444
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• 2014

Lactic acid bacteria (LAB) are probiotics that provide numerous beneficial effects on the host body, especially on the intestine. Combining several strains of LAB, we prepared a formulation containing four different LAB and studied its anti-inflammatory activity both in vitro and in vivo. The formulation significantly reduced NO production from RAW 264.7 cells treated with bacterial lipopolysaccharide, indicating that the formulation might include anti-inflammatory activity. The formulation also suppressed inflammatory change induced by trinitrobenzene sulfonic acid (TNBS) in mice, where oral or rectal administration of the formulation protected the colon tissue from the damage by TNBS. Expressions of the IL-6 and FasL genes appeared to be down-regulated by the formulation in TNBS-treated colon tissues, suggesting that the suppression of those genes may be involved in the anti-inflammatory activity of the formulation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.677-683
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• 2005

The aim of this study was to investigate the apoptotic effect and its mechanism on Radix Aconiti (RA) extract in HL-60 human leukemia cell line. RA extract induced apoptosis as confirmed by discontinuous fragmentation of DNA. To clarify the mechanisms on RA extract-induced apoptosis, we examined the caspase-3, -8 enzyme activity and protein levels including Fas, FasL in HL-60 cells. Treatment with RA extracts resulted in the increase of caspase-3 enzyme activity in a time and dose-dependent manners, which was accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP). This activation of caspase-3 enzyme resulted from cleavage of procaspase-8, which was followed by increases of FasL, Fas protein expression in RA extracts-treated HL-60 cells. In conclusion, RA extract induced apoptosis of HL-60 human leukemia cell line. This results suggest that the apoptotic mechanisms of RA extract on HL-60 cells involved in FasL, Fas activation, procaspase-8 cleavage, activation of caspase-3 and cleavage of PARP. Collectively, these results suggest that RA may be a valuable agent as a anti-cancer drug.