• Molecules and Cells
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• v.42 no.3
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• pp.210-217
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• 2019

The maintenance of mitochondrial function is closely linked to the control of senescence. In our previous study, we uncovered a novel mechanism in which senescence amelioration in normal aging cells is mediated by the recovered mitochondrial function upon Ataxia telangiectasia mutated (ATM) inhibition. However, it remains elusive whether this mechanism is also applicable to senescence amelioration in accelerated aging cells. In this study, we examined the role of ATM inhibition on mitochondrial function in Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) cells. We found that ATM inhibition induced mitochondrial functional recovery accompanied by metabolic reprogramming, which has been known to be a prerequisite for senescence alleviation in normal aging cells. Indeed, the induced mitochondrial metabolic reprogramming was coupled with senescence amelioration in accelerated aging cells. Furthermore, the therapeutic effect via ATM inhibition was observed in HGPS as evidenced by reduced progerin accumulation with concomitant decrease of abnormal nuclear morphology. Taken together, our data indicate that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease.

• BMB Reports
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• v.52 no.3
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• pp.208-213
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• 2019

Chemoresistance is the primary obstacle in the treatment of locally advanced and metastatic nasopharyngeal carcinoma (NPC). Recent evidence suggests that the transcription factor forkhead box M1 (FoxM1) is involved in chemoresistance. Our group previously confirmed that FoxM1 is overexpressed in NPC. In this study, we investigated the role of FoxM1 in cisplatin resistance of the cell lines 5-8F and HONE-1 and explored its possible mechanism. Our results showed that FoxM1 and NBS1 were both overexpressed in NPC tissues based on data from the GSE cohort (GSE12452). Then, we measured FoxM1 levels in NPC cells and found FoxM1 was overexpressed in NPC cell lines and could be stimulated by cisplatin. MTT and clonogenic assays, flow cytometry, ${\gamma}H2AX$ immunofluorescence, qRT-PCR, and western blotting revealed that downregulation of FoxM1 sensitized NPC cells to cisplatin and reduced the repair of cisplatin-induced DNA double-strand breaks via inhibition of the MRN (MRE11-RAD50-NBS1)-ATM axis, which might be related to the ability of FoxM1 to regulate NBS1. Subsequently, we demonstrated that enhanced sensitivity of FoxM1 knockdown cells could be reduced by overexpression of NBS1. Taken together, our data demonstrate that downregulation of FoxM1 could improve the sensitivity of NPC cells to cisplatin through inhibition of MRN-ATM-mediated DNA repair, which could be related to FoxM1-dependent regulation of NBS1.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6485-6488
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• 2014

Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.572-584
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• 2022

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

• Membrane Journal
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• v.8 no.3
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• pp.170-176
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• 1998

A study on the bioconversion of soluble starch to cyclodextrin(CD) homologue by CGTase was performed in the membrane-enzyme reactor equipped with a dead-end type membrane module. in the batch reactor, the total conversion of soluble starch to CD homologue was decreased rapidly from a maximum value of 45 % with increasing reaction time due to the product inhibition and breakdown of CD homologue to the reducing sugars. However, in the membrane-enzyme reactor, the total conversion of soluble starch was maintained at a constant value of 35 % throughout the reaction, since the membrane(MWCO = 10,000) promptly separated CD homologue from the reaction mixture. After the macdon for 24 hr in the membrane-enzyme reactor using a 10 % soluble starch solution, the cumulative production amount of CD homologue was about 3.7 kg/m$^2$ at the operating pressure of 2 atm.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.52-52
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• 2021

Persicaria amphibia as an England native plant, is a rhizomatous perennial, one of the rather amphibious plants. Its aquatic form contains water-soluble sugars, starch, and protein. P. amphibia have up to 18% tannins in stems and rhizomes. Previous studies have confirmed the anti-inflammatory activity of live bacteria roots, but no studies on bioactivity are known. DNA damage responses (DDRs) pathways are considered a crucial factor affecting the alleviation of cellular damage. The ataxia-telangiectasia mutated and Rad3 related (ATM) and checkpoint kinase 2 (Chk2) pathways are the main pathways of DNA damage response. Also, p53 is a key integrator of cellular response to oxidative DNA damage, contributing repair, or leading transcription including apoptosis. In the present study, we conducted an investigation into the inhibitory effects of P. amphibia on oxidative DNA damage for confirming potential to complementary medicine and therapies. In conclusion, P. amphibia can provide protective effects against double-stranded DNA break (DSB) caused by oxidative DNA damage.

• Bulletin of the Korean Chemical Society
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• v.35 no.5
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• pp.1379-1384
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• 2014

${\alpha}-Fe_2O_3$ spherical particles having an average diameter of ca. 420 nm and ${\alpha}-Fe_2O_3$ fine particles (< 10 ${\mu}m$ particle size) were prepared to examine as catalysts for CO oxidation. Kinetic studies on the catalytic reactions were performed in a flow reactor using an on-line gas chromatography system operated at 1 atm. The apparent activation energies and the partial orders with respect to CO and $O_2$ were determined from the rates of CO disappearance in the reaction stage showing a constant catalytic activity. In the temperature range of $150-275^{\circ}C$, the apparent activation energies were calculated to be 13.7 kcal/mol on the ${\alpha}-Fe_2O_3$ spherical submicron clusters and 15.0 kcal/mol on the ${\alpha}-Fe_2O_3$ fine powder. The Pco and $Po_2$ dependencies of rate were investigated at various partial pressures of CO and $O_2$ at $250^{\circ}C$. Zero-order kinetics were observed for $O_2$ on both the catalysts, but the reaction order for CO was observed as first-order on the ${\alpha}-Fe_2O_3$ fine powder and 0.75-order on the ${\alpha}-Fe_2O_3$ spherical submicron clusters. The catalytic processes including the inhibition process by $CO_2$ on the ${\alpha}-Fe_2O_3$ spherical submicron powder are discussed according to the kinetic results. The catalysts were characterized using XRD (X-ray powder diffraction), FE-SEM (field emission-scanning electron microscopy), HR-TEM (high resolution-transmission electron microscopy), and $N_2$ sorption measurements.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7043-7048
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• 2014

Inhibition of heat shock protein 90 (Hsp90) leads to inappropriate processing of proteins involved in DNA damage repair pathways after DNA damage and may enhance tumor cell radio- and chemotherapy sensitivity. To investigate the potentiation of antitumor efficacy of lidamycin (LDM), an enediyne agent by the Hsp90 inhibitorgeldanamycin (GDM), and possible mechanisms, we have determined effects on ovarian cancer SKOV-3, hepatoma Bel-7402 and HepG2 cells by MTT assay, apoptosis assay, and cell cycle analysis. DNA damage was investigated with H2AX C-terminal phosphorylation (${\gamma}H2AX$) assays. We found that GDM synergistically sensitized SKOV-3 and Bel-7402 cells to the enediyne LDM, and this was accompanied by increased apoptosis. GDM pretreatment resulted in a greater LDM-induced DNA damage and reduced DNA repair as compared with LDM alone. However, in HepG2 cells GDM did not show significant sensitizing effects both in MTT assay and in DNA damage repair. Abrogation of LDM-induced $G_2/M$ arrest by GDM was found in SKOV-3 but not in HepG2 cells. Furthermore, the expression of ATM, related to DNA damage repair responses, was also decreased by GDM in SKOV-3 and Bel-7402 cells but not in HepG2 cells. These results demonstrate that Hsp90 inhibitors may potentiate the antitumor efficacy of LDM, possibly by reducing the repair of LDM-induced DNA damage.

• Korean Chemical Engineering Research
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• v.44 no.2
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• pp.121-128
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• 2006

Propylene epoxidation by $H_2O_2$ (30％ aqueous) as oxidant was studied in a semi-batch reactor using TS-1 catalyst: Effects of reaction temperature, time, pressure, solvent, catalyst and $H_2O_2$ concentration on $H_2O_2$ conversion (limiting reagent) and product distribution were investigated. Potential inhibition by propylene oxide on the epoxidation rate was also examined. Ti-MCM-22 with MWW zeolytic structure was found to exhibit better performance than TS-1 with MFI structure, provide that a proper choice of solvent(acetonitrile) is made.