• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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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.

• 대한약침학회지
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• 제4권1호
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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.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1999년도 한국생물과학협회 학술발표대회
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• pp.166.1-166
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• 1999

No Abstract, See Full Text

• Toxicological Research
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• 제19권3호
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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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• 제2권2호
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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.

• 대한한의학회지
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• 제25권2호
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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.

• 한국식품과학회지
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• 제36권4호
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• pp.669-676
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• 2004

본 연구는 젖산균과 효모에 의해 발효처리한 감귤의 기능적 특성을 파악하고자 수행되었다. 발효감귤 추출물의 항산화도는 발효하지 않은 감귤 추출물과 비교할 때 뚜렷하게 증가하였다. 또한, 대조구와 비교할 때 발효처리한 감귤 추출물에서 플라보노이드 조성변화가 나타났으며, 각각 naringenin, hesperetin의 농도가 증가하였다. 감귤은 발효처리와 상관없이 HepG2 세포의 세포사멸 보호효과를 나타내었으나, 발효처리구에서 세포사멸 보호효과와 ROS(Reactive oxygen species) 생성 감소효과가 더욱 차별적으로 나타났다. 수컷의 Sprague-Dawley rat에 감귤 추출물과 발효감귤 추출물을 경구 투여하였다, 체중은 다른 실험군에 비해 발효감귤 추출물의 고농도 투여(100 mg/kg 체중)에서 유의적으로 감소하였고 혈장 콜레스테롤 함량은 다소 감소하였으나, 다른 실험구에 비하여 유의적인 차이는 나타나지 않았다. 고지방 식이에 의해 유도된 지방간 형성은 발효 감귤 추출물 투여에 의해 유의하게 감소되었다. 본 연구 결과는 발효 감귤 추출물은 세포수준에서 감귤추출물에 비해 증강된 세포 사멸 보호효과와 항산화 효과를 나타내며, 동물실험에서는 고 지방 식이에 의해 유도된 지방간 형성을 저해하는 효과를 보여 주었다.

• 생명과학회지
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• 제19권6호
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• pp.799-803
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• 2009

방사선 및 각종 독성물질에 의한 고환 정세관세포의 사멸은 apoptosis와 관련이 있다고 알려져 있으나 정세관상피주기에 따른 apoptosis 발생에 대한 변화연구는 미진하다. 본 연구에서는 감마선을 조사한 ICR 마우스의 고환에서 apoptosis 발생을 transferase-mediated end labeling (TUNEL) 과 periodicacid-Schiff (PAS) 염색을 동시에 실시하여 관찰하였다. Apptosis는 TUNEL 양성으로 나타났으며 특징적 형태변화를 보였다. 2 Gy (분당 2 Gy의 선량률)의 방사선을 조사하고 24시간동안의 변화를 관찰한바 방사선조사 후 12시간에 가장 높은 apoptosis 발생을 보였고 이후 감소하였다. 8 Gy까지의 방사선을 조사하고 8시간에 변화를 관찰한 결과 모든 정세관상피주기에서 방사선 용량에 비례한 apoptosis의 발생이 관찰되었다. 방사선 용량-반응은 linear-quadratic 곡선 [y=(-0.014${\pm}$0.009)$D^{2}$ +(0.31${\pm}$0.697)D+0.3575. Y는 정세관 당 TUNEL 양성세포의 수, D는 방사선 용량(Gy), $r^{2}$=0.9]에 가장 일치 하였다. 최대반응은 8 Gy에서 관찰되었으며, 0.5 Gy조사군에서도 변화가 나타났다. 이러한 변화는 정세관상피주기 V에서 B정조세포와 정세관상피주기 XII의 분열기 정자세포에서 가장 현저하였다.

• Biomolecules & Therapeutics
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• 제22권3호
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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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• 제50권1호
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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.