• 한국식품과학회지
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• 제34권1호
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• pp.114-117
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• 2002

연교의 메탄올 추출물로부터 caspase 저해물질을 분리하였으며, ESI-MS, $^1H-NMR$, $^13C-NMR$, DEPT 등의 기기분석 자료에 의하여 rengyolone으로 동정하였다. 이 물질은 $IC_{50}\;6.25\;{\mu}g/mL$의 농도에서 etoposide가 처리된 U937 세포주의 caspase-3 유도 저해를 나타내었다. 또한 rengyolone은 $Interleukin-1{\beta}$가 처리된 D10S 세포에서 caspase-1의 유도저해활성을 나타내었으며, $IC_{50}$값은 $7.5\;{\mu}g/mL$이었다.

• BMB Reports
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• 제34권6호
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• pp.544-550
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• 2001

In pre-transplant total-body irradiation (TBI), the lung is a critical dose-limiting organ. Also, the possible role of oxidative stress was suggested in the development of TBI-induced lung damage. This study explores the association between TBI-induced oxidative stress and the induction of lung pathogenesis by investigating TBI-induced oxidative stress in the lungs of male C57BL/6 mice after a single dose of 10 Gy TBI. We showed significant increases of reactive oxygen species (ROS) formation and lipid peroxidation, and also a depletion and oxidation of glutathione after TBI. There is evidence that pretreatment with 1,10-phenanthroline (o-phen) significantly reduces oxidative stress in the lung. This indicates that the TBI-induced ROS generation involves a metal-catalyzed Fenton-type reaction. A pretreatment of buthionine sulfoximine (BSO) augmented the glutathione depletion and oxidation, but had no effect on the ROS formation and lipid peroxidation up to 6 h after TBI. Histopathological features that are consistent with pneumonitis were observed in the BSO pretreated-mice 1 week after irradiation. The results suggest that TBI-induced oxidative stress in the lung involves a generation of ROS through a Fenton-type reaction. Also, glutathione plays an important inhibitory role in the radiation-induced lung pathogenesis by participating in the self-amplifying cascade subsequent to the ROS generation by irradiation.

• International Journal of Oral Biology
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• 제43권2호
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• pp.61-68
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• 2018

Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• 대한약침학회지
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• 제17권1호
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• pp.59-69
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• 2014

Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

• 대한한방내과학회지
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• 제24권1호
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• pp.104-112
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• 2003

Objectives : The purpose of this study is to evaluate the effects of Sohaphyang-won and is to study the mechanism for neuronal death protection in hypoxia with Embryonic day 20(E20) cortical cells of a guinea pig(Sprague Dawley). Methods : E20 cortical cells, used in this investigation were dissociated in Neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Sohaphyang-won was added to the culture media for 72 hours. On 17 DIV, cells were given a hypoxic shock and further incubated in normoxia for another three days. On 20 DIV, Sohaphyang-won's effects for neuronal death protection were evaluated by LDH assay and the mechanism was studied by Bcl-2, Bak, Bax, caspase family. Results : This study indicates that Sohaphyang-won's effects for neuronal death protection in hypoxia is confirmed by LDH assay by the method of Embryonic day 20(E20) cortical neuroblast. Conclusions : Sohaphyang-won's mechanism for neuronal death protection in hypoxia restrains inflow of cytochrome C into cellularity caused by Bcl-2 increase and reduces the caspase cascade initiator caspase-10 and the effector caspase-3.

• Journal of Ginseng Research
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• 제22권2호
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• pp.126-132
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• 1998

In the present study, we examined effects of ginseng saponins (ginsenosides) on pp60c-src protein tyrosine kinase (PTK) activity, intracellular calcium concentration ([$Ca^{2+}$]i), and cell proliferation in NIH3T3 cells. Eight different ginsenosides [ginsenoside-Rb1 (G-$Rb_1$), -$Rb_2$, -Rc, -Rd, -Re, -Rf, -$Rg_1$, -$Rg_2$) and ginseng total saponin (GTS) were used for these experiments. All ginsenosides and GTS tested stimulated the activation of $pp60^{c-src}$ kinase, and especially G-$Rb_1$,-Rd,-$Rg_1$, and -$Rg_1$ showed a higher stimulatory effect than others at 16.7 $\mu\textrm{g}$/ml of ginsenosides with a 18 hr-incubation, increasing the activity by 4.5, 3.5, 3.5, and 3.0-fold, respectively, over that of untreated control. In addition, both G-Rd and -$Rg_2$)Rg2 increased ($Ca^{2+}$), to 202 and 334 nM, respectively, about 2-3-fold above the basal level within 7min at 250 $\mu\textrm{g}$/yml of ginsenosides. The increases of ($Ca^{2+}$), were eliminated by Pretreatment of EGTA, an extracellular calcium chelator, suggtasting that they result from an influx of calcium ion from extracellular medium rather than an efflux from intracellular calcium store, endoplasmic reticulum (ER). All ginsenosides studied enhanced cell proliferation to 1.2-1.4-fold over that of untreated control at 5~250 $\mu\textrm{g}$/ml of concentrations. Interestingly the promotion of cell proliferation by ginsenosides corresponded with the activation of c-src kinase, which is an early step in the mitogenic signaling cascade. Taken together, we suggest that some ginsenosides may lead to cellProliferation via the activation of cellular signal transduction Pathway involving $pp60^{c-src}$ kinase.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• Animal cells and systems
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• 제4권3호
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• pp.279-285
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• 2000

Vitamin E-succinate (VES) treatment of U937 human monoblasts induced cells to undergo apoptosis. After 96 h of VES treatment at 10 $\mu$/ml, more than 80% of cells appeared apoptotic. Evidence for apoptosis by VES was based on propidium iodide staining for detection of chromatin condensational fragmentation and electrophoretic DNA ladder formation. Western blot analyses showed a transient increase in Fas and p21 protein levels up to 48 h alter the VES treatment. Protein expression and activity of CDK1 and lamin B degradation were remarkably induced by VES, following the cleavage of caspase-3 after 48 h. The VES-induced apoptosis was found to involve activation of PKC as shown by increases in membrane translocation of PKC$\beat$II and PKC activity. Pretreatment of GF109203X (PKC inhibitor) prior to VES treatment almost completely inhibited the induction of apoptosis as assessed by blockage of VES-induced caspase-3 activity and DNA fragmentation. However, GF109203X h8d no effect on the VES-induced nitric oxide synthesis, which was required for monocvtic differentiation in our previous report (J Cell Sci 111, 435, 1998). Taken together, our data suggest that induction of apoptosis by VES in U937 cells occurs through activation of PKC-$\beat$II resulting in the activation of caspase-3 cascade and is independent of nitric oxide.

• 대한기계학회논문집
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• 제14권5호
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• pp.1311-1319
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• 1990

본 연구에서는 작동유체로서 습증기와 거동이 유사한 습증기를 대기흡입식 간 헐 초음속 풍동을 이용하여, 팽창율이 일정한 노즐을 통하여 팽창시키는 경우에 대하 여 비평형 응축영역내 입치하는 경우에 대하여, 정체점 상태량의 변화에 기인되는 응 축 및 응축형격파가 경사형격파의 형상과 변화에 미치는 영향을 다음의 관점으로부터 연구하였다.

• 대한기계학회논문집B
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• 제25권3호
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• pp.414-421
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• 2001

The present study is conducted to investigate the local heat/mass transfer characteristics on the shroud with blade tip clearances. The relative motion between blade and shroud has little influence on the overall heat transfer characteristics, except some local effects. Therefore, the relative motion between the blade and shroud is neglected in this study. A naphthalene sublimation method is employed to determine the detailed local heat/mass transfer coefficients on the surface of the shroud. The tip clearance is changed from 0.66% to 2.85% of the blade chord length. The flow enters the gap between the blade tip and shroud at the pressure side due to the pressure difference. Therefore, the heat/mass transfer characteristics on the shroud are changed significantly from those with endwall. At first, high heat/mass transfer occurs along the profile of blade at the pressure side due to the entrance effect and acceleration of the gap flow. Then, the heat/mass transfer coefficients on the shroud increase along the suction side of the blade because tip leakage vortices are generated and interact with the main flow. The results show that the heat/mass transfer characteristics are changed largely with the gap distance between the tip of turbine blade and the shroud.