• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3857-3862
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• 2012

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

• Journal of Pharmacopuncture
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• v.4 no.1
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• pp.123-124
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• 2001

Purpose. Free radicals are implicated in the pathophysiology of aging, ischemic injury and neurodegenerative disorders. To deform]no whether Hominis Placenta extract prevents $H_2O_2$-induced apoptosis, we have performed morphological and biochemical analyses for the detection of apoptotic phenomena in the pineal tumor cell line $PGT-{\beta}$ We have also peformed cytochemical and immunocytochemical analyses for the detection of changes in nitric oxide synthase (NOS) activity and estimated the expression . of apoptotic genes using reverse transcription-polymerase chain reaction (RT-PCR) Methods. $PGT-{\beta}\;cells$ were pretreated with Hominis Placenta extracts $(0,\;10^{-2}\;{\mu}g/ml)$ for 2 hours and then exposed to $H_2O_2\;(0,\;50\;{\mu}M)$ for 3 hours. Appearance of apoptotic characteristics were monitored using 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI) staining assay, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay and flow cytometric analysis. NOS activity was measured by NADPH-diaphorase cytochemistry. Expression of inducible NOS (iNOS) and nuclear factor kappa B (NF k B) was assessed via immunocytochemistry. The expression of apoptotic genes was examined by RT-PCR. Results. After 3 flours of exposure to $H_2O_2$, it was shown that $PGT-{\beta}\;cells$ treated with $H_2O_2(50\;{\mu}M)$ exhibit classical apoptotic features and increases in NOS activity and caspase-3 expression. Treatment with Hominis Placenta extract resulted in a reduced occurrence of apoptotic features. DAPI staining, TUNEL and flow cytometric assays revealed decreases in the occurrence of nuclear fragmentation and in the sub-Gl fraction in the $PGT-{\beta}\;cells$ treated with Hominis Placenta extract. Cells treated with Hominis Placenta extract also showed lower activity of NADPH-diaphorase and immunoreactivities of both iNOS and NF k B than those of $H_2O_2$-treated cells which were not treated with Hominis Placenta extract. By RT-PCR, it was shown that the level of caspase-3 mRNA was derreased In the cells treated with Hominis Placenta . extract. Conclusions. This study shows that Hominis Placenta extract prevents $H_2O_2$-induced apoptosis in $PGT-{\beta}\;cells$; inhibitions of iNOS and caspnse-3 are possible mechanisms of the protection against apoptosis.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.166.1-166
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• 1999

No Abstract, See Full Text

• Toxicological Research
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• v.19 no.3
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• pp.197-203
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• 2003

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.65-71
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• 2002

The immunological mechanism of the responses to ultraviolet (UV) B radiation in mouse models were investigated by the suppression of contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH), and susceptibility to infection. However, there are some differences in immune suppression according to the different models as well as the irradiation protocols. Therefore, this review focused on the differences in the suppressive effects on CHS and DTH, and susceptibility to infection in relation to the different in vivo models. Recent advances in cytokine knockout mice experiments have the reexamination of the role of the critical cytokines in UVB-induced immune suppression, which was investigated previously by blocking antibodies. The characteristics of the suppressor cells responsible for UVB-induced tolerance were determined. The subcellular mechanism of UVB-induced immune suppression was also explained by the induction of apoptotic cells through the Fas and Fas-ligand interaction. The phagocytosis of the apoptotic cells is believed to induce the production of the immune suppressive cytokine like interleukin-10 by macrophages. Therefore, the therapeutic UVB response to a skin disease, such as psoriasis, by the depletion of infiltrating T cells could be considered in the extension line of apoptosis and immune suppression.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.67-76
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• 2004

Objectives : This study was designed to investigate the protective mechanisms of Palmul-tang on hypoxia-induced cytotoxicity in H9c2 cardiomyoblast cells. Methods : In this study, we used H9c2 cells. Cells were subjected to hypoxia in the absence and presence of $1000\mu\textrm{g}/ml$ Palmul-tang for 24 hrs. Cells were treated with various concentrations of Palmul-tang for 24 hrs. Cell viability was measured by MTT assay. Hypoxia markedly decreased the viability of H9c2 cells, which was characterized with apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. Results : Palmul-tang significantly reduced hypoxia-induced cell death and apoptotic characteristics. Also, Palmul-tang prevented mitochondrial dysfunction including the disruption of mitochondrial membrane permeability transition (MPT) and an increase in expression of apoptogenic Bcl-2 proteins in hypoxia-H9c2 cells. Conclusions; This study suggests that the protective effects of Palmul-tang against hypoxic damages may be mediated by the modulation of Bcl-2, Bax expression.

• Korean Journal of Food Science and Technology
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• v.36 no.4
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• pp.669-676
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• 2004

Functional characteristics of citrus products fermented with lactic acid bacterium and yeast were investigated. Flavonoid composition of fermented citrus extracts increased significantly compared to control, leading to increases of naringenin and hesperetin concentrations. All citrus extracts showed anti-apoptotic effects in HepG2 cells regardless of fermentation, with citrus-fermented products showing greater anti-apoptotic effect and intracellular Reactive Oxygen Species content reduction compared to native citrus extracts. Male Sprague-Dawley rats were orally dosed with native or fermented citrus extracts. Singnificantly higher body weight reductions were observed in higher fermented citrus-dosed (100 mg/kg body weight) group compared to the other groups. Plasma total cholesterol level was slightly, but not significantly, reduced. Fatty liver formation induced by high-fat diet was significantly suppressed in rats administered with fermented citrus extracts. Results suggest fermented citrus extracts have potent anti-apoptotic and anti-oxidative activities in vitro, and inhibitory activity against fatty liver formation by high-fat diet in vivo.

• Journal of Life Science
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• v.19 no.6
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• pp.799-803
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• 2009

The killing of male germ cells by radiation and other toxicants has recently been attributed to apoptosis, but a critical evaluation of the presence of the different features of apoptosis in each epithelial stage has not been performed. In this study, mouse testes exposed to radiation were examined by light microscopy and terminal transferase-mediated end labeling (TUNEL) with periodic acid-Schiff (PAS) stains to determine whether the cells were apoptotic according to several criteria. Apoptosis was easily recognized by the presence of peroxidase-stained, entirely apoptotic bodies. In the TUNEL-positive cells or bodies, the stained products correlated precisely with the typical morphologic characteristics of apoptosis as seen at the light microscopic level. The changes that occurred from 0 to 24 hours after exposing the mice to 2 Gy of gamma-rays (2 Gy/min) were examined. The numbers of apoptotic cells reached a peak at 12 hours after irradiation and then declined. The mice that received 0-8 Gy of gamma-rays were examined 8 hours after irradiation. Dose-response relationships were generated for each stage of the epithelial cycle by counting TUNEL-positive cells. The dose-response curves were linear- quadratic [y=(-0.014${\pm}$0.009)$D^{2}$+(0.31${\pm}$0.697)D+0.3575. Where y=the number of apoptotic cells per seminiferous tubule, and D=the irradiation dose in Gy, $r^{2}$=0.9] and there was a significant relationship between the frequency of apoptotic cells and the radiation dose. Although the maximum response was produced by 8 Gy, even 0.5 Gy induced marked changes. These changes were most pronounced in B spermatogonia of stage V and the spermatocyte at the mitotic cells of stage XII.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.184-192
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• 2014

${\beta}$-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of ${\beta}$-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. ${\beta}$-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in ${\beta}$-lapachone-treated AGS cells. Treatment with ${\beta}$-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished ${\beta}$-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by ${\beta}$-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased ${\beta}$-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of ${\beta}$-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to ${\beta}$-lapachone-mediated AGS cell growth inhibition and apoptosis induction.

• Parasites, Hosts and Diseases
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• v.50 no.1
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• pp.1-6
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• 2012

$Toxoplasma$ $gondii$ penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with $T.$ $gondii$ through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of $T.$ $gondii$-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with $T.$ $gondii$ disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that $T.$ $gondii$ induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves.