• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.431-438
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• 2006

Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.203-213
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• 2018

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

• Microbiology and Biotechnology Letters
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• v.41 no.4
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• pp.407-415
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• 2013

In this study, we investigated the antioxidant activities on HaCaT and the whitening effects on B16F1 melanoma cells of Dendropanax morbifera leaf extract. In an antioxidative activity assay using HaCaT cells, the ethyl acetate ($50{\mu}g/ml$) and aglycone fractions ($25{\mu}g/ml$) of the D. morbifera leaf extract didn't exhibit any characteristics of cytotoxicity. When HaCaT cells were exposed to a single large dose ($800mJ/cm^2$) of UVB, the extracts protected the cells against UVB radiation. When HaCaT cells were treated with 10 mM $H_2O_2$ and $4{\mu}M$ rose bengal, the ethyl acetate ($6.25{\sim}50{\mu}g/ml$) and aglycone ($6.25{\sim}25{\mu}g/ml$) fractions protected the cells against oxidative damage in a concentration dependent manner. When the whitening effects of D. morbifera leaf extract were tested in melanoma B16/F1 cells treated with the a-melanocyte stimulating hormone (${\alpha}$-MSH), the extracts inhibited ${\alpha}$-MSH-stimulated intra/extracellular melanogenesis in a concentration dependent manner. The inhibitory effects of the ethyl acetate and aglycone fractions of D. morbifera leaf extract were 21% and 44% at $25{\mu}g/ml$, respectively. Both are more effective than arbutin (15% at $25{\mu}g/ml$) which is known as a whitening agent. These results indicate that fractions of the D. morbifera leaf can function as cell protectants and natural antioxidants in biological systems, particularly skins exposed to UV radiation by quenching and/or scavenging $^1O_2$ and other ROS, and protecting cells against ROS. In addition, fractions of the D. morbifera leaf can be applied to new whitening cosmetics because of their inhibitory effects on ${\alpha}$-MSH stimulated melanogenesis in B16F1 melanoma cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.33 no.3
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• pp.145-152
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• 2007

In this study, the antioxidative effects of Sueada asparagoides and Salicornia herbacea extracts were investigated. The free radical(1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity($FSC_{50}$) of extract/fractions of Sueada asparagoides was in the order: 100 % ethanol extract(329.33 ${\mu}g/mL$) < 50 % ethanol extract(40.73) < ethylacetate fraction(13.87) < deglycosylated aglycone fraction (7.80). In case of Salicornia herbacea, the free radical scavenging activities of ethylacetate fraction and aglycone fraction were 13.87 and 7.80 ${\mu}g/mL$, respectively. Reactive oxygen species(ROS) scavenging activities($OSC_{50}$) of Sueada asparagoides and Solicornia herbacea extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activity of Sueada asparagoides extracts was 50 % ethanol extract($OSC_{50}$, $0.99{\mu}g/mL$) < ethylacetate fraction (0.05) < aglycone fraction (0.03). Aglycone fraction showed the most prominent scavenging activity. In case of Salicornia herbacea, the ROS scavenging activities of ethylacetate fraction and aglycone fraction were 0.10 and 0.20 ${\mu}g/mL$, respectively. The protective effects of extract/fractions of Sueada asparagoides and Salicornia herbacea on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The ethanol extract(100%) of Sueada asparagoides diminished photohemolysis in a concentration dependent manner($1{\sim}100{\mu}g/mL$). Particularly deglycosylated aglycone fraction exhibited the most prominent celluar protective effect($\tau_{50}$, 310 min at 50 ${\mu}g/mL$). In case of Salicornia herbacea, ethylacetate fraction exhibited more potent protective effect. These results indicate that extract/fractions of Sueada asparagoides can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.34 no.4
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• pp.259-268
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• 2008

In this study, the antioxidative effects, inhibitory effects on tyrosinase and elastase and components of Castanea crenata leaf were investigated. The free radical (1,1-diphenyl-2-picrylhydrazyl radical, DPPH) scavenging activity ($FSC_{50}$) of extract / fractions of Castanea crenata left was in the order: 50% ethanol extract ($13.6{\mu}g/mL$) < ethyl acetate fraction (6.2) < aglycone fraction (2.1). Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$ of extract / fractions from Castanea crenata leaf extract / fractions on ROS generated in $Fe^{3+}$-EDTA/$H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activity was in the order: aglycone fraction (0.8) < 50% ethanol extract (0.5) < ethyl acetate fraction (0.3). The scavenging activity ($IC_{50}$ for ${O_2}^{{\cdot}\;-}$ (superoxide anion radical) generated by NBT method was in the order: ethyl acetate fraction (145.5) < aglycone fraction (65.5). The protective effects on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The ethyl acetate fraction exhibited the most prominent cellular protective effect (${\tau}_{50}$, $191.9{\pm}12.2\;min$ at $10{\mu}g/mL$). The inhibitory effect of aglycone fraction ($9.1{\mu}g/mL$) on elastase was higher than oleanolic and ($13.7{\mu}g/mL$). And the inhibitory effect of aglycone fraction ($21.6{\mu}g/mL$) on tyrosinase was higher than arbutin ($226.2{\mu}g/mL$). But 50% ethanol extract rarely exhibited the inhibitory activity on tryosinase and elastase. Flavonoids were contained in Castanea crenata left (96.3 mg / 100 g dried Castanea crenata leaf). And flavonoids contained in ethyl acetate fraction were kaempferol, quercetin, quercitrin, and so on. Quercitrin is the most abundant component. These results indicate that extract / fractions of Castanea crenata can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging free radical and ROS, Castanea crenata leaf extract/ fractions could be used as new cosmeceutical for whitening and anti-wrinkle products.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.130-137
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• 1999

Background: In cardiac surgery, hypothermia is associated with a number of major disadvantage, including its detrimental effects on enzymatic function, energy generation and cellular integrity. Warm cardioplegia with normothermic cardiopulmonary bypass cause three times more incidence of permanent neurologic deficits than the cold crystalloid cardioplegia with hypothermic cardiopulmonary bypass. Interruptions or inadequate distribution of warm cardioplegia may induce anaerobic metabolism and warm ischemic injury. To avoid these problems, tepid blood cardioplegia was recently introduced. Material and Method: To evaluate whether continuous tepid blood cardioplegia is beneficial in clinical practice during valvular surgery, we studied two groups of patients matched by numbers and clinical characteristics. Warm group(37$^{\circ}C$) consisted of 18 patients who underwent valvular surgery with continuous warm blood cardioplegia. Tepid group(32$^{\circ}C$) consisted of 17 patients who underwent valvular surgery with continuous tepid blood cardioplegia. Result: Heartbeat in 100% of the patients receiving continuous warm blood cardioplegia and 88.2% of the patients receiving continuous tepid blood cardioplegia converted to normal sinus rhythm spontaneously after removal of the aortic cross clamp. There were no differences between these two groups in CPB time, ACC time, the amount of crystalloid cardioplegia used and peak level of potassium. During the operation, the total amount of urine output was more in the warm group than the tepid group(2372${\pm}$243 ml versus 1535${\pm}$130 ml, p<0.01). There were no differences between the two groups in troponin T level measured 1hr and 12hrs after the operation. Conclusion: Continuous tepid blood cardioplegia is as safe and effective as continuous warm blood cardioplegia undergoing cardiac valve surgery in myocardial protection.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.1-8
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• 1999

Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

• Journal of Yeungnam Medical Science
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• v.16 no.2
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• pp.228-236
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• 1999

Background: Thyrotoxic periodic paralysis is an uncommon illness characterized by intermittent flaccid paralysis of skeletal muscle, usually accompanied by hypokalemia, in patient with hyperthyroidism. However, the pathophysiology of thyrotoxic periodic paralysis remains largely unexplained and controversial. This report describes the clinical and biochemical findings in 19 patients with thyrotoxic periodic paralysis who were examined at the Yeungnam University Medical Center(YUMC) during the past decade. Methods: The medical records of 997 YUMC patients, seen between 1986 and 1996, with diagnosis of hyperthyroidism were reviewed. Nineteen patients out of 997 hyperthyroidism patients were diagnosed, and examined by history, physical examination, serum electrolyte value, and thyroid function test during paralysis. On the basis of these results, comparisons were made on age, sex, precipitating factors, timing, affected limbs, prognosis, serum potassium and serum phosphate and thyroid hormone levels. Results: The prevalence of periodic paralysis in hyperthyroidism was 1.9 percent and the male to female prevalence ratio was 30:1 and in all patients, the development of perodic paralysis was correlated with hyperfunctional state of the thyroid gland. Eleven cases of periodic paralysis were associated with hypokalemia and their thyroid hormone levels were significantly more increased than those of the patients without hypokalemia. Interestingly, our study shows the recurrence of paralysis after treatment. Conclusion: Although the precise pathophysiology of the disease is as yet undefined and controversial, it occurs primarily in Asians with an overwhelming male preponderance and prevalence of 2 percent in hyperthyroidism. The interactive roles of thyroid hormone, Na-K pump, and genetically inherited defect in the cellular membrane potential of the skeletal muscle can be speculated. Further investigation will be needed to firmly establish the mechanism of thyrotoxic periodic paralysis.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.3
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• pp.235-241
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• 2009

In this study, the antioxidative effects, inhibitory effects on tyrosinase, elastase of Persicaria perfoliata extracts were investigated. The deglycosylated fraction of extract ($12.38{\mu}g$/mL) showed the most prominent free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity ($FSC_{50}$). Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of P. perfoliata extracts on ROS generated in $Fe^{3+}$-EDTA/$H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The ethyl acetate fraction of extract ($0.35{\mu}g$/mL) showed the most prominent ROS scavenging activity. The protective effects of P. perfoliata extract/fractions on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The P. perfoliata extracts suppressed photohemolysis in a concentration dependent manner ($1{\sim}50{\mu}g$/mL) except the deglycosylated fraction of extract. The inhibitory effect of P. perfoliata extracts on tyrosinase was investigated to assess their whitening efficacy. Inhibitory effects ($IC_{50}$) on tyrosinase were determined with ethyl acetate fraction of P. perfoliata extract ($136.00{\mu}g$/mL) and deglycosylated fraction of extract ($68.10{\mu}g$/mL). Finally, their anti-elastase activities were measured to predict the anti-wrinkle efficacy in the human skin. Inhibitory effects ($IC_{50}$) on elastase were determined with ethyl acetate fraction of P. perfoliata extract ($67.20{\mu}g$/mL) and deglycosylated fraction of extract ($43.50{\mu}g$/mL). These results indicate that extract/fractions of P. perfoliata can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS. Extract/fractions of P. perfoliata can be applicable to new functional cosmetics for antioxidant, antiaging.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.3
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• pp.209-217
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• 2009

In this study, the antibacterial activity, antioxidative effects, inhibitory effects on tyrosinase of Inula britannica flower extracts were investigated. MIC values of ethyl acetate fraction from Inula britannica flower on P. acnes 0.25 %, respectively. The results showed that the antibacterial activity of the ethyl acetate fraction was the highest in the P. acnes. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activities ($FSC_{50}$) of ethyl acetate fraction of Inula britannica flower was $8.55{\mu}g$/mL. Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of some fInula britannica flower extracts on ROS generated in $Fe^{3+}$- EDTA/$H_2O_2$ system were investigated using the luminol-dependent chemiluminescence assay. The order of ROS scavenging activities were ethyl acetate fraction $0.24{\mu}g$/mL. Ethyl acetate fraction showed the most prominent ROS scavenging activity. The protective effects of extract/fractions of Inula britannica flower on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. The Inula britannica flower extracts suppressed photohemolysis in a concentration dependent manner ($5{\sim}100{\mu}g$/mL), particularly deglycosylated flavonoid aglycone fraction exhibited the most prominent celluar protective effect ($\tau_{50}$, 164.15 min at $25{\mu}g$/mL). The inhibitory effect of Inula britannica flower extracts on tyrosinase was investigated to assess their whitening efficacy. Inhibitory effects ($IC_{50}$) on tyrosinase of some Inula britannica flower extracts were high. Ethyl acetate fraction has $IC_{50}$ of $87.03{\mu}g$/mL. These results indicate that extract/fractions of Inula britannica flower can function as antioxidants in biological systems, particularly skin exposed to UV radiation by scavenging $^1O_2$ and other ROS, and protect cellular membranes against ROS. And inhibitory activity on tyrosinase of the ethyl acetate fraction and high potential as bactericide against the skin pathogenic bacteria could be applicable to new functional cosmetics for antioxidant, antiaging, antibacterial activity.