• The Korean Journal of Physiology and Pharmacology
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• 제15권6호
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• pp.327-332
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• 2011

It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and diabetic opium-addicted brain and liver cells were significantly higher than the both normal and diabetic rats. In addition, we found that apoptosis in brain cells of opium-addicted and diabetic opium-addicted male rats were significantly higher than opium-addicted and diabetic opium-addicted female, whereas apoptosis in liver cells of opium-addicted and diabetic opium-addicted female rats were significantly higher than opium-addicted and diabetic opium-addicted male. Overall, these results indicate that opium probably plays an important role in brain and liver cells apoptosis, therefore, leading neurotoxicity and hepatotoxicity. These findings also in away possibly means that male brain cells are more susceptible than female and interestingly liver of females are more sensitive than males in induction of apoptosis by opium.

• 약학회지
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• 제53권1호
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• pp.6-11
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• 2009

This study investigated the antiproliferative effect of the EtOH extract from Litsea japonica. The extract markedly inhibited the growth of HL-60 cells. When treated with the extract, several apoptosis events like as DNA fragmentation, chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. The extract decreased the Bcl-2 expression, whereas the Bax expression was increased. Caspase-9 and -3 were activated and poly (ADP-ribose) polymerase was cleaved. The results suggest that the antiproliferative effect of L. japonica in HL-60 appears to arise from apoptosis induction via the down-regulation of Bcl-2 and the activation of caspases.

• 한방재활의학과학회지
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• 제24권2호
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• pp.41-50
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• 2014

Objectives The purpose of this study was to evaluate the effects of Clematidis radix extract on $CoCl_2$-induced apoptosis in SH-SY5Y human neuroblastoma cells. Methods In order to investigate the protective effect of Clematidis radix on $CoCl_2$-induced cytotoxicity in neuronal cells, MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, DAPI(4,6-diamidino-2-phenylindoleI) staining, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) assay, DNA fragmentation assay and western blotting were performed on SH-SY5Y human neuroblastoma cells. Results Cells treated with $CoCl_2$ exhibited several apoptotic features, while cells pre-treated with Clematidis radix prior to $CoCl_2$ exposure showed a decrease in the occurrence of apoptotic features. $CoCl_2$ increased HIF-$1{\alpha}$ expression, in contrast, Clematidis radix treatment decreased $CoCl_2$-induced HIF-$1{\alpha}$ expression. Pre-treatment with the extract of Clematidis radix suppressed Bax, cytochrome c, and caspase-3 expressions, and also increased Bcl-2 expression in SH-SY5Y human neuroblastoma cells. Conclusions These results suggest that Clematidis radix may exert a protective effect on $CoCl_2$-induced apoptosis in SH-SY5Y human neuroblastoma cells.

• Advances in Traditional Medicine
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• 제4권3호
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• pp.171-178
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• 2004

Ginseng radix, the root of Panax ginseng C. A. Meyer (Araliaceae), is a medicinal plant used world-widely and has been reported to have various biological effects. To investigate the effects of Ginseng radix on HL-60 cell apoptosis, MTT assay, DNA fragmentation assay and flow cytometry were performed on HL-60 cells. Cells were treated with Ginseng radix at different concentrations $(10^{-4},\;10^{-3}\;and\;10^{-2};\;dilution\;rate)$. Ginseng radix significantly induced cells apoptosis with a time- and dose-dependent manner. To determine whether Ginseng radix-induced apoptosis is due to increase of tumor necrosis factor $(TNF-{\alpha})$ secretion, enzyme-linked immunosorbent assay was performed on HL-60 cells. Unexpectedly, Ginseng radix $(96\;{\pm}\;5\;pg/ml)$ significantly decreased the $TNF-{\alpha}$ secretion compared with control $(174\;{\pm}\;14\;pg/ml)$. Furthermore, Ginseng radix with $rIFN-{\gamma}$ synergistically increased nitric oxide production in mouse peritoneal macrophages. Taken together, our data indicate that Ginseng radix induce apoptosis on HL-60 cells without increase of $TNF-{\alpha}$ secretion and could be used for a supplementary remedy of cancer.

• Advances in Traditional Medicine
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• 제10권4호
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• pp.254-262
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• 2010

Artemisia capillaris (A. capillaries) is known to play roles in many cellular events, such as cell proliferation, differentiation, and apoptosis. We investigated the antifibrogenic efficacy of A. capillaris in the immortalized human hepatic stellate cell line LX2. Cell proliferation was determined by the MTT assay. Cell cycle was analyzed by the flow cytometry. Apoptotic cells were measured using a cell death detection ELISA. Caspase activity was detected by a colorimetric assay. The mRNA level of Bcl-2 and Bax mRNA were measured by real-time PCR. MEK and ERK protein were detected by Western blot analysis. We provide evidence that A. capillaris induces cell cycle arrest, apoptosis, and potently inhibits the mitogen-activated protein kinase pathway. A. capillaris inhibited cell proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle analysis with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 mRNA levels and an increase in Bax expression. Exposure of LX2 cells to A. capillaris induced caspase-3 activation, but co-treatment of A. capillaris with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. A. capillaris down-regulated Mcl-1 protein levels and inhibited phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.

• 대한본초학회지
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• 제21권4호
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• pp.51-58
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• 2006

Objectives : In this study, we investigate that Ulmi cortex extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Ulmi cortex was extracted from the leaves of the plant using water. The Ulmi cortex extract was treated to different concentrations for 24 hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell cycle inhibition was confirmed by kinases assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Western blot. Results : Exposure to Ulmi cortex extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Ulmi cortex extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Ulmi cortex extract induces G1-cell cycle arrest and DNA fragmentation in HT-29 cells. Furthermore, Ulmi cortex extract induces cell apoptosis through the activation of caspases-3 and PARP cleavage. Conclusion : Ulmi cortex extract induces apoptosis in human colon cancer cells, therefore, we suggest that Ulmi cortex extract can be used as a novel class of anti-cancer drugs.

• BMB Reports
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• 제51권10호
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• pp.538-543
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• 2018

Pancreatic beta cell destruction and dysfunction induced by cytokines is a major cause of type 1 diabetes. Paraoxonase 1 (PON1), an arylesterase with antioxidant activity, has been shown to play an important role in preventing the development of diabetes in transgenic mice. However, no studies have examined the anti-diabetic effect of PON1 delivered to beta cells using protein transduction. In this study, we expressed the cell-permeable PON1 fused with PEP-1 protein transduction domain (PEP-1-PON1) to investigate whether transduced PEP-1-PON1 protects beta cells against cytokine-induced cytotoxicity. PEP-1-PON1 was effectively delivered to INS-1 cells and prevented cytokine-induced cell destruction in a dose-dependent manner. Transduced PEP-1-PON1 significantly reduced the levels of reactive oxygen species (ROS) and nitric oxide (NO), DNA fragmentation, and expression of inflammatory mediators, endoplasmic reticulum (ER) stress proteins, and apoptosis-related proteins in cytokine-treated cells. Moreover, transduced PEP-1-PON1 restored the decrease in basal and glucose-stimulated insulin secretion induced by cytokines. These data indicate that PEP-1-PON1 protects beta cells from cytokine-induced cytotoxicity by alleviating oxidative/nitrosative stress, ER stress, and inflammation. Thus, PEP-1-mediated PON1 transduction might be an effective method to reduce the extent of destruction and dysfunction of pancreatic beta cells in autoimmune diabetes.

• 동의생리병리학회지
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• 제16권6호
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• pp.1143-1150
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• 2002

Recent evidence suggests that many Oriental Medicinal prescriptions are effective in cancer patients as a supportive care. Oriental Medicinal herbs have been investigated extensively and are known to have multiple pharmacological effect. These herbs contain a variety of ingredients which may act synergistically to inhibit tumor cell division, to increase tumor cell death (apoptosis), and to increase the proportion of immune cells within tumor. Paljinhangahm-dan (Paljin) has been used to treat for cancer patients in Oriental Medicine for decades. The effects of aqueous extract of Paljin on the induction of apoptotic cell death were investigated in human leukemia cell lines (HL-60, Jurkat, Molt-4 and U937). The viability of leukemia cells was markedly decreased by Paljin in a dose-dependent manner. Paljin induced the apoptotic death of leukemia cells, which was characterized by the ladder-pattern DNA fragmentation, and chromatin condensation of the nuclei. Paljin digested Bid protein but did not affect Bcl-2 protein level and also, induced mitochondrial dysfunction disrupted as shown as the mitochondrial membrane potential. It activated caspase-9 and caspase-3. thereby resulted in cleavage of poly(ADP) ribose polymerase(PARP). These results indicate that Paljin induces apoptosis of human leukemia cells via activation of intrinsic caspase cascades with mitochondrial dysfunction.

• 동의생리병리학회지
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• 제17권3호
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• pp.751-758
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• 2003

In our previous studies, we reported that Selaginella Tamariscina(ST) induced apoptotic cell death in HL-60 cells selectively. The cell viability after treatment with extract of ST was quantified by MTT assay and trypan bleu exclusion method. The results showed that application with ST in HL-60 induced 40% cell death at the concentration of 400 ㎍/ml. The cancericidic effect of Selaginella Tamariscina was mediated by apoptosis. Thus, HL-60 cells exposed to Selaginella Tamariscina displayed the DNA fragmentation ladder and nucleus chromatin condensation characteristic for apoptosis. The enzyme activity of caspase-3 and actived caspase-3 protein were markedly increased in HL-60 cells treated with the extract of Selaginella Tamariscina. In addition, the extract of Selaginella Tamariscina induced cleavage of PARP, a known substrate for caspase-3. The expression of Bcl-2, anti-apoptotic protein, was decreased by treatment of the aqueous extract of Selaginella Tamariscina in a dose-dependent manner. And the expression of pro-apoptotic Bax protein was increased. In conclusion, our results suggest that the extract of Selaginella Tamariscina may induce the apoptotic death of HL-60 cells via activation of caspase-3, cleavage of PARP protein, depletion of cellular ATP levels and Bcl-2 degradation.

• 동의신경정신과학회지
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• 제21권2호
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• pp.29-44
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• 2010

Objectives : The purpose of this study was to investigate the effect of Gentianae Radix on neurogenesis and apoptosis in ethanol- induced newborn rats hippocampus dentate gyrus. Methods : In vivo, laboratory animals were divided into three groups; Normal group(N), Control group(C) and Treated group (TG)(n=7 for each group). N were treated saline daily for five days. C were treated 1.5 g/kg ethanol and saline daily for five days. TG were treated 1.5 g/kg ethanol and 300 mg/kg Gentianae Radix daily for five days. BrdU(5-bromo-2-deoxyuridine) assay was used to test neurogenesis in the dentate gyrus. And TUNEL(Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was used to test apoptosis in the dentate gyrus. Three groups were measured body weight, serum ethanol concentration, BrdU-positive cells and TUNEL-positive cells in the dentate gyrus. In vitro, MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to test viability in SK-N-MC cells. BrdU assay was used to test neurogenesis in SK-N-MC cells. DNA fragmentation and caspase-3 enzyme activity assay were used to test apoptosis in SK-N-MC cells. And treated ethanol and Gentianae Radix of all in vitro tests were made various concentration. Results : In vivo, Gentianae Radix modulated ethanol-induced neurogenesis and apoptosis in newborn rats hippocampus dentate gyrus. In vitro, TG 100 ${\mu}g/ml$ have significantly modulated ethanol-induced neurogenesis and apoptosis in SK-N-MC cells. And only TG 100 ${\mu}g/ml$ have significantly protected SK-N-MC cells from ethanol-induced cytotoxicity. Conclusions : Gentianae Radix may have the effect that modulated ethanol-induced neurogenesis and apoptosis in SK-N-MC cells.