• Archives of Plastic Surgery
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• v.32 no.3
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• pp.369-375
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• 2005

Apoptosis is a physiologic or programmed cell death process which is controlled by genes. It is essential for the function and the appropriate development of multicellular organism. It is also thought to be one of the main mechanisms of cell death in ischemic tissues. The effect of prostaglandin $E_1$($PGE_1$) is proven to be useful in the recovery of ischemic changes by inducing vasodilation of peripheral vessels and platelet disaggregation. $PGE_1$ is also known to suppress apoptosis in human liver sinusoidal endothelial cell from ischemia-reperfusion injury. The purpose of this study is to evaluate the effects of $PGE_1$ on the apoptosis in the ischemia reperfusion injury of rat intestine. Thirty Sprague-Dawley rats were used. In control group(N=15), superior mesenteric artery was occluded for 60 minutes and after removing the vessel clamp, it was reperfused for 60 minutes and harvested. In experimental group(N=15), a jejunal flap was also made as in the control group except for the intraarterial administration of the $PGE_1$ right after clamping the artery and removing the clamp. H&E, TUNEL and immunohistochemical stains for p53, bax, and bcl-2 were performed. There were ischemic changes in gross and microscopic findings in both groups. The apoptotic index was significantly lower in the experimental group($1.29{\pm}0.82$(p=0.003)) than in the control group ($2.33{\pm}0.95$). The rat intestinal ischemia apoptosis by ischemia-reperfusion was partly related to the modulating of bcl-2, bax, and p53 expression. Our results indicate that $PGE_1$ suppresses the apoptosis in the ischemic jejunal flap and this effect is probably the result of a increase in expression of bcl-2.

• Applied Microscopy
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• v.37 no.4
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• pp.239-248
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• 2007

Alteration of temperature is one of cancer therapies. In general, severe hyperthermia(around $43^{\circ}C$) and hypothermia(around $18^{\circ}C$) trigger apoptosis through mitochondria, though the specific mechanism is still unknown. CC-t6 and GB-d1 cell lines, which were originally derived from human cholangiocarcinoma and gall bladder cancer, were established from a metastatic lymph node. To investigate the mechanism of metastatic cancer cell response to thermal stresses, hyperthermia($37^{\circ}C{\rightarrow}43^{\circ}C$) and hypothermia($37^{\circ}C{\rightarrow}17.4^{\circ}C$) were designed. Thermal stresses did not induce apoptosis but necrotic cell death. Any alterations of caspase-3, -9, cytochrome c, Bax, and Bcl-2 were not found in both hyperthermia and hypothermia exposed fells using western blot analysis. In the transmission electron microscopy, typical necrotic, but not apoptotic, changes were observed. These results suggest that temperature changes induce cell death through necrotic pathway in metastatic cancer in vitro, and it can be one of effective anticancer methods.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.254-263
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• 2010

Objectives : The neuroprotective effects of bee venom (BV) have been demonstrated in many studies, but bee venom has many side effects. So we used sweet bee venom (SBV), which has high molecular elements removed to reduce the side effects. I examined the neuroprotective effect of sweet bee venom in 1-methyl-4-phenylpyridine ($MPP^+$)-induced human neuroblastoma SH-SY5Y cells. Methods : To observe the possible toxicity of SBV itself, SH-SY5Y cells were treated with SBV in various concentrations for 3 h and $MPP^+$ in concentrations (1 and 5mM) for 24h. To investigate the protective effect of SBV against $MPP^+$ toxicity, SH-SY5Y cells were pretreated with vehicle or nontoxic concentrations of SBV for 3h and the cells were not washed, followed by incubation with respective concentrations of SBV and 1 mM $MPP^+$ for 24h. To investigate the protective effect of SBV against $MPP^+$ toxicity, SH-SY5Y cells were pretreated with vehicle or nontoxic concentrations of SBV for 3h and the cells were not washed, followed by incubation with respective of SBV(0.5%), 1 mM $MPP^+$, 5uM AKT inhibitor(LY984002) and 10uM ERK inhibitor(PD98059) for 24 h. The protective effect was measured by cell viability assay. To investigate the degree of apoptosis, caspase-3 enzyme activity was measured in control, $MPP^+$, SBV+$MPP^+$. Results : SBV (0.5%) pretreatment protected the SH-SY5Y cells against $MPP^+$-induced apoptotic cell death. The cell viability was higher in the SH-SY5Y cells that were pretreated with vehicle or nontoxic concentrations of SBV than those not pretreated. The caspase-3 activity was lower in the pretreated groups than these not pretreated. ERK and AKT enzymes have a role in the neuroprotective effects of the sweet bee venom. Conclusions : The results demonstrate that SBV has a protective effect on dopaminergic neurons against $MPP^+$ toxicity. This data suggest that SBV could be a potential therapeutic tool for neurodegenerative diseases such as Parkinson's disease(PD).

• Journal of Life Science
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• v.27 no.11
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• pp.1349-1356
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• 2017

Potassium channel openers (KCOs) produce physiological and pharmacological defense mechanisms against cell injuries caused by oxidative stress of diverse origins. Openings of mitochondrial and plasmalemmal $K^+$ channels are involved in the defense mechanisms. This study tested whether NS 1619, an opener of large-conductance BK channels, has a similar beneficial influence on the pigment epithelial cells of retinas. The human retinal pigment epithelial cell line ARPE-19 was exposed to $H_2O_2$-induced oxidative stress in the absence and presence of NS 1619. The degrees of the cells' injuries were assessed by analyzing the cells' trypan-blue exclusion abilities and TUNEL staining. NS 1619 produced remarkable protections against cell injuries caused by $H_2O_2$. It prevented apoptotic and necrotic cell deaths. The protective effect of NS 1619 was significantly diminished when the cells were treated with NS 1619 in combination with the BK channel-blocker paxilline. NS 1619 significantly ameliorated cellular ATP deprivations in $H_2O_2$-treated cells. It helped mitochondria preserve their functional integrity, which was estimated by their MTT reduction abilities and mitochondrial membrane potential. In conclusion, it was suggested that NS 1619 had a beneficial effect on mitochondria in regards to preserving their functional integrity under oxidative stress, and it produces defense mechanisms against oxidant-induced cell injuries in ARPE-19 cells.

• Journal of Acupuncture Research
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• v.31 no.1
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• pp.111-119
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• 2014

Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.

• The Korea Journal of Herbology
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• v.20 no.3
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• pp.29-41
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• 2005

Objectives : The use of natural products with therapeutic properties is as ancient as human civilisation and, for a long time, mineral, plant and animal products were the main sources of drugs. Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniceae) has been shown to possess anti-microbial and anti-tumoral properties. Heme oxygenase-1 (HO-1) is a stress response protein and is known to play a protective role against the oxidative injury. In this study, we examined whether catalposide could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 protein expression and HO activity. We also examined the effects of catalposide on the productions of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. Methods : HO-1 expression in Neuro 2A cells was measured by Western blotting analysis. NO and $TNF--{\alpha}$ produced by RAW 264.7 macrophage were measured by Griess reagent and enzyme-linked immunosorbent assay, respectively. Results : The treatment of the cells with catalposide resulted in dose- and time-dependent up-regulations of both HO-1 protein expression and HO activity. Catalposide protected the cells from hydrogen peroxide-induced cell death. The protective effect of catalposide on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX, a HO inhibitor. Additional experiments revealed the involvement of CO in the cytoprotective effect of catalposide-induced HO-1. In addition, catalposide inhibited the productions of $TNF--{\alpha}$ and NO with significant decreases in mRNA levels of $TNF--{\alpha}$ and inducible NO synthase. Conclusions : Our results indicate that catalposide is a potent inducer of HO-1 and HO-1 induction is responsible for the catalposide-mediated cytoprotection against oxidative damage and that catalposide may have therapeutic potential in the control of inflammatory disorders.

• Journal of Oral Medicine and Pain
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• v.30 no.2
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• pp.231-238
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• 2005

Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.

• Journal of Life Science
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• v.23 no.12
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• pp.1509-1515
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• 2013

The term lipotoxicity has been used to describe how excess lipid accumulation leads to cellular dysfunction and death in non-adipose tissues, including skeletal muscle. While lipotoxicity has been found in cultured skeletal muscle cells with high-fat feeding, the consequences of lipotoxicity in vivo are still unknown, particularly in Type-I muscle, which is metabolically affected by lipotoxicity. The aim of this study was to investigate the effects of a high-fat diet on changes in the morphology and apoptotic protein expression of Type-I muscle loss in rats. The rats were fed either a high-fat diet or a normal diet for six weeks, and then lipid accumulation, inflammation response, and nucleus infiltration were measured, and PARP protein expression was cleaved by Oil Red O staining, H & E staining, and Western blot, respectively. Lipid accumulation, inflammation response, nucleus infiltration, and cleaved PARP protein expression were significantly (p<0.05) higher in the high-fat diet group than they were in the normal diet group. The weight of Type-I muscle tended to be lower in the high-fat diet group compared to the normal diet group, but the difference was not statistically significant. These results indicate that a high-fat diet triggers cell death in Type-I muscle via lipotoxicity, which suggests that a high-fat diet may be associated with sarcopenia.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.112-112
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• 2019

Baicalein is one of the main flavonoids derived from roots of Scutellaria baicalensis Georgi, a traditional Oriental medicine. Although baicalein has high antitumor effect on several human carcinomas, the mechanism responsible for this property is not unclear. In this study, the data revealed that baicale-ininduced growth inhibition was associated with the induction of apoptosis connecting with cytochrome c release, down-regulation of anti-apoptotic Bcl-xl and increased the percentage of cells with a loss of mitochondria membrane permeabilization. Baicalein also induced the proteolytic activation of caspases and cleavage of PARP; however, blockage of caspases activation by z-VAD-fmk inhibited baicalein-induced apoptosis. In addition, baicalein enhanced the formation of autophagosomes and up-regulated LC3-II/LC3-I ratio. Interestingly, the pretreatment of bafilomycin A1 recovered baicalein-induced cell death suggesting that autophagy by baicalein roles as protective autophagy. Taken together, our results indicated that this flavonoid induces apoptosis and cell protective autophagy. These data means combination treatment with baicalein and autophagy inhibitor might be a promising anticancer drug.

• Journal of Life Science
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• v.10 no.1
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• pp.57-63
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• 2000

${\beta}$-catenin, which plays a critical role in both the cytoskeleton and in transcriptional regulation in variousadherent cell types, undergoes degradation during adherent cell apoptosis. Although ${\beta}$-catenin has been reported to be present in Jurkat T-acute lymphoblastic leukemia cells, the regulation of ${\beta}$-catenin in hematologic malignancies have not been examined. The data presented here demonstrate that treatment of the T cell leukemia Jurkat iwht the apoptosis inducer anti-Fas induced proteolytic cleavage of ${\beta}$-catenin. ${\beta}$-catenin was cleaved at both the N- and C-terminus after anti-Fas treatment. Cleavage of intact ${\beta}$-catenin was completely inhibited by caspase selective protease inhibitors. These data demonstrate that ${\beta}$ -catenin proteolysis is triggered by the cross-linking of the Fas receptor on Jurkat cells and subsequent activation of caspase protease. There was a clear accumulatio of the large proteolytic fragment in Jurkat cells treated with lactacystin of ALLM. These are potent inhibitors of proteasome and calpain. these results suggest that both the proteasome and clapain may recognize the large ${\beta}$-catenin fragment as a substrate fot further degradation and that these pathewasy may act downstream of scapase in response to Fas receptor activation. Therefore, we suggest that ${\beta}$-catenin may play a role in promoting Jurkat survival.