• BMB Reports
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• 제34권3호
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• pp.189-193
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• 2001

Curcumin a yellow pigment from Curcuma Tonga, has been known to possess antioxidative and anticarcinogenic properties, as well as to induce apoptosis in some cancer cells. There have been, however, several contradictory reports that hypothesized curcumin (a hydrophobic molecule) can bind a membrane Gpid bilayer and induce nonspecific cytotoxicity in some cell lines. Why curcumin shows these contradictory effects is unknown. In A-431 cells, growth inhibition by curcumin is due mostly to the specific inhibition of the intrinsic tyrosine kinase activity of the epidermal growth factor receptor, as reported earlier by Korutla et al. Thus, we assumed that the cell death of A-431 by curcumin might be due to the specific induction of apoptosis. In this paper we clearly show that curcumin induces apoptosis in A-431 cells. The cureumin-induced cell death of A-431 exhibited various apoptotic features, including DNA fragmentation and nuclear condensation. Furthermore, the curcumin-induced apoptosis of A-431 cells involved activation of caspase-3-like cysteine protease. Involvement of caspase-3 was further confirmed by using a caspase-3 specific inhibitor, DEVD-CHO. In another study, decreased nitric oxide (NO) production was also shown in A-431 cells treated with curcumin, which seems to be the result of the inhibition of the iNOS expression by curcumin, as in other cell lines. However, 24 h after treatment of curcumin there was increased NO production in A-431 cells. This observation has not yet been clearly explained. We assumed that the increased NO production may be related to denitrosylation of the enzyme catalytic site in caspase-3 when activated. Taken together, this study shows that the cell death of A-431 by curcumin is due to the induction of apoptosis, which involves caspase-3 activation.

• Molecules and Cells
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• 제37권9호
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• 한국의사학회지
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• 제19권2호
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• pp.29-47
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• 2006

Because the size of population was directly related to the power of the nation in the Chosun Dynasty, various efforts were exerted to maintain the size stable and the keys to the efforts were a high birth rate and a low death rate. However, in addition to wars, epidemic diseases had an enormous effect on the death rate. Particularly during the mid Chosun Dynasty, epidemic diseases were more prevalent than ever due to the abnormal climate called the little ice age. To cope with them, the government executed several medical relief policies and published medical books. In Chinese epidemiology, infectious diseases mean sicknesses caused by hot weather, but in Korean epidemiology, they indicate large-scale infectious sicknesses caused by both hot and cold weather. Therefore, as treatment methods for diseases from the cold were not applicable to the pathology of epidemic diseases, China developed separate epidemiology. In Korea, however, the main concern was how to prevent epidemic diseases, whether from hot or cold weather, that drove many lives into death. The characteristics of Korean epidemiology are as follows. First, whenever epidemic diseases were prevalent, in order to cope with them, translated medical books were promptly published including Ganibyeokonbang, Bunmunonyeokihaebang, Sinchanbyeokonbang, Byeokyeoksinbang and Byeokonsinbang. Second, those books were annotated in Korean so that people could read easily and accurately. Third, as an extension of the Hyangyak movement from the late Koryo Dynasty, Danbang was used a lot to treat and prevent epidemic diseases with less financial burden, and things obtainable easily according to individuals' situation were mentioned for anybody to overcome the emergent situation of epidemic diseases. Fourth, methods for praying to God were suggested for practitioners to work with sincere spirit and to keep themselves from epidemic diseases.

• 동의생리병리학회지
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• 제18권1호
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• pp.101-109
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• 2004

Spatholobus suberectus belonging the family Leguminosae has been used for promoting blood circulation, removing blood stasis, tonifying the blood, relaxing tendons, stopping internal bleeding and eliminating dampness in oriental traditional medicine. This study investigates whether the water extracts of S. suberectus induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by S. suberectus, as measured by cell morphology. The capability of S. suberectus to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP­ribose)polymerase protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of S. suberectus on cell cycle progression. G1 checkpoin related gene products tested (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2Fl) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by S. suberectus may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• 대한임상독성학회지
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• 제16권1호
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• pp.1-8
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• 2018

Purpose: Extremely hazardous pesticides are classified as World Health Organization (WHO) hazard class Ia. However, data describing the clinical course of WHO class Ia OP (organophosphate) poisonings in humans are very scarce. Here, we compare the clinical features of patients who ingested hazard class Ia OPs. Methods: This retrospective observational case study included 75 patients with a history of ingesting ethyl p-nitrophenol thio-benzene phosphonate (EPN), phosphamidon, or terbufos. The patients were divided according to the chemical formulation of the ingested OP. Data regarding mortality and the development of complications were collected and compared among groups. Results: There were no differences in the baseline characteristics and severity scores at presentation between the three groups. No fatalities were observed in the terbufos group. The fatality rates in the EPN and phosphamidon groups were 11.8% and 28.6%, respectively. Patients poisoned with EPN developed respiratory failure later than those poisoned with phosphamidon and also tended to require longer mechanical ventilatory support than phosphamidon patients. The main cause of death was pneumonia in the EPN group and hypotensive shock in the phosphamidon group. Death occurred later in the EPN group than in the phosphamidon group. Conclusion: Even though all three drugs are classified as WHO class Ia OPs (extremely hazardous pesticides), their clinical courses and the related causes of death in humans varied. Their treatment protocols and predicted outcomes should therefore also be different based on the chemical formulation of the OP.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.163-169
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• 2007

The neurotoxicity of amyloid $\beta(A\beta)$ is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While(-)-epigallocatechin-3-gallate(EGCG) suppresses $A\beta$-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival system such as protein kinase C(PKC), extracellular-signal-related kinase(ERK), c-Jun N-terminal kinase(JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One ${\mu}M\;A{\beta}_{1-42}$ decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG($1{\mu}M$) significantly attenuated $A{\beta}_{1-42}$-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by $A{\beta}_{1-42}$ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the $A{\beta}_{1-42}$-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against $A{\beta}_{1-42}$-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4587-4592
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• 2012

Purpose: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) neuroblastoma (NB) and other peripheral nerve cell tumors (PNCT) outcome data. This study found under usage of radiotherapy in these patients. Materials and methods: This study analyzed socio-economic, staging and treatment factors available in the SEER database for NB and other PNCT. For the risk modeling, each factor was fitted by a generalized linear model to predict the outcome (soft tissue specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate the modeling errors. Risk of neuroendocrine (other endocrine including thymus as coded in SEER) death was computed for the predictors. Results: There were 5261 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 83.8 (97.6) months. The mean (SD) age was 18 (25) years. About 30.45% of patients were un-staged. The SEER staging has high ROC (SD) area of 0.58 (0.01) among the factors tested. We simplified the 4-layered risk levels (local, regional, distant, un-staged/others) to a simpler 3-tiered model with comparable ROC area of 0.59 (0.01). Less than 50% of PNCT patients received radiotherapy (RT) including the ones with localized disease. This avoidance of RT use occurred in adults and children. Conclusion: The high under-staging rate may have precented patients from selecting definitive radiotherapy (RT) after surgery. Using RT for, especially, adult PNCT patients is a potential way to improve outcome.

• Journal of Preventive Medicine and Public Health
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• 제34권3호
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• pp.183-190
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• 2001

Objective : To estimate the annual economic costs attributable to cigarette smoking in Korea. Methods : The costs were classified as being direct medical and non-medical costs, indirect costs and others. We focused on those costs related that are incurred in the treatment of selected diseases (cardiovascular diseases, respiratory diseases, and cancers), which have been proven to be caused by smoking. In addition to the basic costs of treatment, the additional amount of costs occurred due to smoking was obtained by computing the population attributable risk (PAR%) caused by smoking. To compute the PAR%, relative risks of smoking to the number of outpatient visits, hospitalizations, and the death were estimated using the Cox proportional hazard model, respectively. Our major data source was the 'Korea Medical Insurance Corporation (KMIC) cohort study,' which was composed of a total of 115,682 male and 67,932 female beneficiaries who had complete records of their smoking histories in the year of 1992. Results : The annual costs that could be attributable to smoking were estimated to be in the range of 2,847,500 million Won to 3,959,100 million Won. The maximum estimate of 3,959,100 million Won includes 233,100 million Won for medical costs, 5,100 million Won for transportation costs, 27,600 million Won for care giver's economic costs, 69,100 million Won in productivity loss, 3,435,000 million Won lost because of premature death, 172,100 million Won in costs resulting from passive smoke inhalation and 17,100 million Won for costs that resulted from fires that were caused by careless smoking. Conclusion : Our study confirms that the magnitude of the economic burden of smoking to Korean society is substantial. Therefore, this study provides strong evidence that there is a strong need for a national policy of tobacco control in Korea.

• 생물정신의학
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• 제8권1호
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• pp.3-19
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• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.101-101
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• 2018

Resveratrol is a polyphenolic compound, which is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. Although several studies have demonstrated that resveratrol possesses anti-cancer activity against various types of human cancer, the molecular mechanisms of resveratrol-mediated overcome drug resistance potential are unclear. In this study, we determined whether resveratrol attenuates drug resistance responses in 5-fluorouracil-resistant colon cancer (SNUC5/5-FUR) cells. Treatment with resveratrol significantly enhanced apoptosis in a concentration-dependent manner, which was associated with the modulation of anti- and/or pro-apoptotic protein expression, activation of caspases and activation of AMP-activated protein kinase. Resveratrol treatment also increased the induction of autophagy through up-regulation of autophagy-related genes such as Microtubule-associated protein 1A/1B-light chain 3, P62 and beclin-1. However, blocking of autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that resveratrol-induced autophagy functions as a cell death mechanism in SNUC5/5-FU cells. Although the further studies are needed, these findings suggest that resveratrol may have therapeutic potential to overcome drug resistance in colon cancer patients.