• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3301-3306
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• 2015

Nucleolin (C23) is an important anti-apoptotic protein that is ubiquitously expressed in exponentially growing eukaryotic cells. In order to understand the impact of C23 in radiation therapy, we attempted to investigate the relationship of C23 expression with the radiosensitivity of human non-small cell lung cancer (NSCLC) cells. We investigated the role of C23 in activating the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), which is a critical protein for DNA double-strand breaks (DSBs) repair. As a result, we found that the expression of C23 was negatively correlated with the radiosensitivity of NSCLC cell lines. In vitro clonogenic survival assays revealed that C23 knockdown increased the radiosensitivity of a human lung adenocarcinoma cell line, potentially through the promotion of radiation-induced apoptosis and adjusting the cell cycle to a more radiosensitive stage. Immunofluorescence data revealed an increasing quantity of ${gamma}$-H2AX foci and decreasing radiation-induced DNA damage repair following knockdown of C23. To further clarify the mechanism of C23 in DNA DSBs repair, we detected the expression of DNA-PKcs and C23 proteins in NSCLC cell lines. C23 might participate in DNA DSBs repair for the reason that the expression of DNA-PKcs decreased at 30, 60, 120 and 360 minutes after irradiation in C23 knockdown cells. Especially, the activity of DNA-PKcs phosphorylation sites at the S2056 and T2609 was significantly suppressed. Therefore we concluded that C23 knockdown can inhibit DNA-PKcs phosphorylation activity at the S2056 and T2609 sites, thus reducing the radiation damage repair and increasing the radiosensitivity of NSCLC cells. Taken together, the inhibition of C23 expression was shown to increase the radiosensitivity of NSCLC cells, as implied by the relevance to the notably decreased DNA-PKcs phosphorylation activity at the S2056 and T2609 clusters. Further research on targeted C23 treatment may promote effectiveness of radiotherapy and provide new targets for NSCLC patients.

• 한국동물학회지
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• 제25권2호
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• pp.55-62
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• 1982

발생 12일째의 계배근세포를 약 7일간 배양하면서 자외선에 의한 절제회복, 광재활성 및 DNA 복제억제율을 조사하여 다음과 같은 결과를 얻었다. 자외선에 의한 절제회복은 계배근세포의 분화정도가 진행됨에 따라 감소하였으며, 이는 특히 자외선의 선량이 높을수록 뚜렷하였다. DNA 합성율은 분화가 진행된 세포일수록 현저히 감소하는 경향이었으며 각 분화단계에 따른 DNA 복제억제 현상은 배양 초기 세포인 경우 자외선 조사후 30분에서 1시간반 사이에서 가장 심하게 나타났고, 배양후기의 세포에서는 이러한 억제현상이 뚜렷하지 않았다. 또 배양 1일째 세포에서 광재활성에 의한 피리미딘 이량체의 감소율은 자외선 조사직후에 현저하였다가 그후 시간의 경과에 따른 차이는 보이지 않았다. 그러나, 절제회복만에 의한 이량체의 감소는 조사후 시간이 지남에 따라 서서히 감소하여 광재활성에 의한 이량체의 감소량과 비슷한 수준으로 접근하였다.

• Fisheries and Aquatic Sciences
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• 제21권10호
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• pp.33.1-33.11
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• 2018

As a process for commercial application, production of reducing sugar, antioxidant, and DNA protective compounds from shrimp-shell powder was investigated in a fed-batch biodegradation using Bacillus cereus EW5. The fed-batch biodegradation was operated in a 5-L bioreactor for 96 h according to three times pulse-feeding strategy. On the basis of the equal working volume (3 L), the fed-batch biodegradation showed a better production of the target compounds than the batch biodegradation, with higher cell density and shortened biodegradation period. The maximum values of the target compounds were 0.297 mg/mL of reducing sugar, 92.35% DPPH radical scavenging activity, 98.16% ABTS radical scavenging activity, and 1.55 reducing power at $A_{700}$, which were approximately 12.1, 3.4, 5.2, and 8.4% enhanced, respectively, compared with those obtained from the batch biodegradation. The fed-batch culture supernatant also showed the enhanced DNA damage inhibition activity than the batch culture supernatant. As a result, the fed-batch biodegradation accompanied by high cell density could produce more useful compounds, enabling an increase in the reutilization value of shrimp-shell waste.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.114-114
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• 2003

p53 has identified as a tumor suppressor protein to protect cells from DNA damage. p53, also well known for a transcription factor, can activate genes such as p21, bax, gadd45 and induce a number of the responses such as differentiation, senescence, DNA repair, apoptosis and the inhibition of angiogenesis to protect cells. Many mechanisms of p53 activation have been studied.(omitted)

• 대한한의학회지
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• 제23권3호
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• pp.33-42
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• 2002

Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6273-6280
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• 2013

Goniothalamin, a natural compound extracted from Goniothalamus sp. belonging to the Annonacae family, possesses anticancer properties towards several tumor cell lines. This study focused on apoptosis induction by goniothalamin (GTN) in the Hela cervical cancer cell line. Cell growth inhibition was measured by MTT assay and the $IC_{50}$ value of goniothalamin was $3.2{\pm}0.72{\mu}g/ml$. Morphological changes and biochemical processes associated with apoptosis were evident on phase contrast microscopy and fluorescence microscopy. DNA fragmentation, DNA damage, caspase-9 activation and a large increase in the sub-G1 and S cell cycle phases confirmed the occurrence of apoptosis in a time-dependent manner. It could be concluded that goniothalamin show a promising cytotoxicity effect against cervical cancer cells (Hela) and the cell death mode induced by goniothalamin was apoptosis.

• 한국식품영양과학회지
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• 제36권12호
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• pp.1628-1632
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• 2007

진달래 꽃 50 g에 1 L의 네 가지 용매(메탄올, 에탄올, 아세톤, 물)를 각각 가하여 추출한 다음, 농축하여 각각의 용매별 추출물을 얻었다. 이 용매별 추출물을 이용하여 진달래꽃의 항산화 활성을 조사하였다. 그 결과, 총 페놀 함량(TPC)은 물 추출물이 328.1 mg/g GAE로 가장 높았고, DPPH 라디칼 소거능(RSA)은 아세톤 추출물의 $IC_{50}$값이 $78{\mu}g/mL$으로 가장 낮은 값을 가지는 것으로 나타났으며, 환원력(RP)의 경우에는 메탄올, 에탄올, 아세톤 추출물의 $IC_{50}$값이 각각 469, 449, $454{\mu}g/mL$으로 ascorbic acid($IC_{50}$: $428{\mu}g/mL$)와 비슷하게 높은 활성을 보임을 알 수 있었다. 그리고 산화적 DNA 손상 보호효과를 측정한 결과 메탄올과 아세톤 추출물은 $1{\mu}g/mL$에서 $50{\mu}g/mL$의 농도로 처리한 결과 유의적으로 DNA 손상정도가 감소하였고, 물 추출물의 경우에는 $5{\mu}g/mL$ 처리구부터 음성대조구의 DNA 손상정도와 비슷한 DNA 손상 보호효과를 보여주었다. 따라서 진달래 꽃 추출물이 천연 항산화제로서의 잠재적 가능성을 가지고 있음을 알 수 있었다.

• Preventive Nutrition and Food Science
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• 제15권4호
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• pp.255-261
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• 2010

Ischemic stroke, a major cause of death and disability worldwide, is caused by occlusion of cerebral arteries that, coupled with or without reperfusion, results in prolonged ischemia (hypoxia and hypoglycemia) and, ultimately, brain damage. In this study, we examined whether methanol extract of the whole plant of Cassia mimosoides var. nomame Makino that grows naturally in Korea, as well as Japan and China, and some of its fractions obtained by partitioning with organic solvents could protect human hepatocellular carcinoma cells (HepG2) under hypoxic condition by inhibiting apoptosis. We also investigated if these extracts could attenuate brain damage in a rat model of 2 hr of ischemia, generated by middle cerebral artery occlusion, and 22 hr of reperfusion. The whole extract ($100{\mu}g$/mL) maintained the cell number at more than half of that initially plated, even after 24 hr of cell culture under hypoxic condition (3% $O_2$). In the absence of the whole extract, almost all of the cells were dead by this time point. This improvement of cell viability came from a delay of apoptosis, which was confirmed by observing the timing of the formation of a DNA ladder when assessed by gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA), butanol and water, EA extracts were selected for the animal experiments, as they improved cell viability at the lowest concentration ($10{\mu}g$/mL). The whole extract (200 mg/kg) and EA extract (10 and 20 mg/kg) significantly reduced infarct size, a measure of brain damage, by 34.7, 33.8 and 45.2.0%, respectively, when assessed by 2,3,5-triphenyl tetrazolium chloride staining. The results suggest that intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic stroke through inhibition of brain cell apoptosis.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.329-340
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• 2024

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H₂O₂). The results showed that mangiferin attenuated H₂O₂-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H₂O₂-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H₂O₂-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.210-215
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• 2013

Ionizing radiation can induce cellular oxidative stress through the generation of reactive oxygen species, resulting in cell damage and cell death. The aim of this study was to determine whether the antioxidant effects of the flavonoid fisetin (3,7,3',4'-tetrahydroxyflavone) included the radioprotection of cells exposed to ${\gamma}$-irradiation. Fisetin reduced the levels of intracellular reactive oxygen species generated by ${\gamma}$-irradiation and thereby protected cells against ${\gamma}$-irradiation-induced membrane lipid peroxidation, DNA damage, and protein carbonylation. In addition, fisetin maintained the viability of irradiated cells by partially inhibiting ${\gamma}$-irradiation-induced apoptosis and restoring mitochondrial membrane potential. These effects suggest that the cellular protective effects of fisetin against ${\gamma}$-irradiation are mainly due to its inhibition of reactive oxygen species generation.