• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.975-982
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• 2015

Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.591-599
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• 2023

Fisetin is a bioactive flavonol molecule and has been shown to have antioxidant potential, but its efficacy has not been fully validated. The aim of the present study was to investigate the protective efficacy of fisetin on C2C12 murine myoblastjdusts under hydrogen peroxide (H₂O₂)-induced oxidative damage. The results revealed that fisetin significantly weakened H₂O₂-induced cell viability inhibition and DNA damage while blocking reactive oxygen species (ROS) generation. Fisetin also significantly alleviated cell cycle arrest by H₂O₂ treatment through by reversing the upregulation of p21WAF1/CIP1 expression and the downregulation of cyclin A and B levels. In addition, fisetin significantly blocked apoptosis induced by H₂O₂ through increasing the Bcl-2/Bax ratio and attenuating mitochondrial damage, which was accompanied by inactivation of caspase-3 and suppression of poly(ADP-ribose) polymerase cleavage. Furthermore, fisetin-induced nuclear translocation and phosphorylation of Nrf2 were related to the increased expression and activation of heme oxygenase-1 (HO-1) in H₂O₂-stimulated C2C12 myoblasts. However, the protective efficacy of fisetin on H₂O₂-mediated cytotoxicity, including cell cycle arrest, apoptosis and mitochondrial dysfunction, were greatly offset when HO-1 activity was artificially inhibited. Therefore, our results indicate that fisetin as an Nrf2 activator effectively abrogated oxidative stress-mediated damage in C2C12 myoblasts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.5
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• pp.857-862
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• 2011

The purpose of this study is to investigate the anti-proliferative mechanism by Trichosanthes kirilowii (TCK) in MCF-7 human breast carcinoma cell. In this study, we used human breast cancer cell line, Michigan cancer foundation-7 cells (MCF-7 cells). They were co-incubated with 30~200 ${\mu}g$/ml TCK for 48 hours, and cell viability was measured by Water-soluble tetrazolium salt-1 (WST-1) assay. After MCF-7 cells were exposed to 60 ${\mu}g$/ml of TCK for 0, 3, 6, 12, 24, 48 hours, We performed flow analysis cytometry sorting(FACS) and western blot analysis. We investigated the effect of dose-dependent cell growth inhibition by TCK, which could be proved by WST-1 assay. Also, flow cytometry analysis showed that TCK increased percentage of subG1 phase and G2/M phase cell cycle. In addition, TCK induced apoptosis through the expression of caspase-9, -3 and poly(ADP-ribose) polymerase(PARP) activation. Moreover, we showed that ATM-dependent G2/M phase arrest by DNA damage and phosphorylation of chk2, cdc25C, cdc2(Tyr15). Taken together, these results suggest that by G2/M phase arrest through DNA damage and inducing of apoptosis through intrinsic pathway, TCK may have potential tumor suppressor in breast cancer.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.138-150
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• 2004

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

• Nutrition Research and Practice
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• v.10 no.4
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• pp.393-397
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• 2016

BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

• Molecules and Cells
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• v.40 no.12
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• pp.906-915
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• 2017

Impairment of wound healing is a common problem in individuals with diabetes. Adiponectin, an adipocyte-derived cytokine, has many beneficial effects on metabolic disorders such as diabetes, obesity, hypertension, and dyslipidemia. C1q/TNF-Related Protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to have beneficial effects on wound healing. In the current study, we demonstrate that CTRP9 regulates growth, differentiation, and apoptosis of HaCaT human keratinocytes. We found that CTRP9 augmented expression of transforming growth factor beta 1 ($TGF{\beta}1$) by transcription factor activator protein 1 (AP-1) binding activity and phosphorylation of p38 in a dose-dependent manner. Furthermore, siRNA-mediated suppression of $TGF{\beta}1$ reversed the increase in p38 phosphorylation induced by CTRP9. siRNA-mediated suppression of $TGF{\beta}1$ or p38 significantly abrogated the effects of CTRP9 on cell proliferation and differentiation while inducing apoptosis, implying that CTRP9 stimulates wound recovery through a $TGF{\beta}1$-dependent pathway in keratinocytes. Furthermore, intravenous injection of CTRP9 via tail vein suppressed mRNA expression of Ki67 and involucrin whereas it augmented $TGF{\beta}1$ mRNA expression and caspase 3 activity in skin of type 1 diabetes animal models. In conclusion, our results suggest that CTRP9 has suppressive effects on hyperkeratosis, providing a potentially effective therapeutic strategy for diabetic wounds.

• Molecules and Cells
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• v.40 no.12
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• pp.916-924
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• 2017

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that $Gadd45{\beta}$ (growth arrest DNA damage-inducible gene $45{\beta}$) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of $Gadd45{\beta}$. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting $Gadd45{\beta}$.

• Biomedical Science Letters
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• v.12 no.3
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• pp.161-170
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• 2006

A new piperazine derivative, 8J-8029, is a synthetic anti-cancer agent which exhibits both microtubule and topoisomerase II inhibiting activities. In this study, we investigated the ability of 8J-8029 for anti-angiogenesis and apoptosis. 8J-8029 decreased the bFGF-induced angiogenesis in the CAM and the mouse Matrigel implants, in vivo. 8J-8029 inhibited the proliferation, migration, invasion, tube fonnation, and expression of MMP-2 in BAECs. In addition, 8J-8029 reduced the cell viability in HepG2 cells, caused the production of fragmented DNA and the morphological changes corresponding to apoptosis. 8J-8029 also elicited the release of cytochrome c and the activation of caspase-3. Taken together, these results suggest 8J-8029 may be a candidate for anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.

• Molecules and Cells
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• v.37 no.12
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• pp.857-864
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• 2014

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.