Hae-Ryong Park

Japanese Foundation for Cancer Research, Edo, Tōkyō, Japan

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Publications (57)85.53 Total impact

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    ABSTRACT: In our study, each part (flesh, white rind, and green rind) of watermelon was extracted using hydrothermal extraction method at temperatures ranging from 100 to at the intervals of 10, 30, and 60 min. We found that hydrothermal treatment has a significant bearing not only on tyrosinase inhibitory activity but also on neuronal cell protection of watermelon parts. The peak tyrosinase inhibitory activity (about 93%) was observed in both the flesh and green rind extracts at for 60 min. In addition, we observed that hydrothermal extracts of watermelon parts at for 60 min also evidenced significant protection effect for neuronal cell against in a concentrationdependent manner. The results of this study confirm that hydrothermal treatment may be an efficient processing method for the purpose of obtaining potent bioactive substances from watermelon.
    Journal of the Korean Society of Food Science and Nutrition 01/2013; 42(10).
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    ABSTRACT: Inhibiting the unfolded protein response (UPR) can be a therapeutic approach, especially for targeting the tumor microenvironment. Here, we show that compound C (also known as dorsomorphin), a small-molecule inhibitor of AMP-activated protein kinase (AMPK) and bone morphogenetic protein (BMP) signaling, inhibit the UPR-induced transcription program depending on the glucose deprivation conditions. We found that compound C prevented UPR marker glucose-regulated protein 78 (GRP78) accumulation and exerted enhanced cytotoxicity during glucose deprivation. Gene expression profiling, together with biochemical analysis, revealed that compound C had a unique mode of action to suppress the transcriptional activation of UPR-targeted genes, as compared with the classic UPR inhibitors versipelostatin and biguanides. Surprisingly, the UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition. We further found that combination treatments of compound C and the classic UPR inhibitors resulted in synergistic cell death with UPR suppression during glucose deprivation. Our findings demonstrate that compound C could be a unique tool for developing a UPR-targeted antitumor therapy.
    PLoS ONE 01/2012; 7(9):e45845. · 3.53 Impact Factor
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    Young-Kyoung Kang, Eun-Ah Lee, Hae-Ryong Park
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    ABSTRACT: In an attempt to identify the neuroprotective effect of Cudrania tricuspidata (CT) leaves against ROS (reactive oxygen species)-induced oxidative stress in neuronal cells, the extracts from CT leaves were investigated using PC12 cells and N18-RE-105 cells. The methanolic and ethanolic extracts from CT were denoted as CTM (Cudrania tricuspidata Leaves methanolic extracts) and CTE (Cudrania tricuspidata Leaves ethanolic extracts), respectively. The neuroprotective effects of the extracts were measured by DCF-DA assay, MTT reduction assay, and LDH release assay. The PC12 cells exposed to -induced oxidative stress and the N18-RE-105 cells exposed to glutamate-induced oxidative stress were treated with various concentrations of CTM and CTE. The results, CTM treatments resulted in the induction of a dose-dependent protective effect in PC12 cells and N18-RE-105 cells. Interestingly, CTE also showed neuroprotective effect in PC12 cells and N18-RE-105 cells. Therefore, these results suggest that CTM and CTE could be a new potential candidate as neuroprotective agents against ROS-induced oxidative stress in neuronal cells.
    Korean journal of food and cookery science. 01/2012; 28(6).
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    ABSTRACT: This study was performed to investigate the physiological activities of stings of Gleditsia sinensis extracts. Antioxidant activity was evaluated by measuring total phenolic contents (TPC), comet assay, and 2.2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA). Anti-diabetic activity was measured by inhibition activities on -glucosidase. Stings of Gleditsia sinensis extracts were prepared by extracting them with methanol and ethanol. The methanolic extracts showed the highest phenol content (1.12 g/100 g gallic acid equivalents). The -glucosidase inhibitory activity of methanol extracts were 17.9% higher, and that of ethanol extracts were 10.3% higher at a concentration of 1 mg/ml. These results indicate that stings of Gleditsia sinensis might be potential candidates as antioxidant and anti-diabetic agents.
    Journal of Life Science. 01/2011; 21(1).
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    ABSTRACT: Postmortem examinations of tissues of humans and rodents with a host of neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, have identified oxidative damage in proteins, lipids, and DNA. The aim of this study was to better understand the cellular mechanisms of neuronal cell degeneration induced via oxidative stress and the protective roles of bioactive substance. In order to achieve this aim, we established a screening program to discover therapeutic agents that exhibit preferential neuroprotective activity in H(2)O(2)-treated PC12 cells. During the course of our screening program, we isolated an active compound, SG-168, from Dendrobium nobile Lindley and identified it as a neuroprotective agent. SG-168 was identified as a compound with an acetal skeleton, a prototypical compound, by electrospray ionization-mass spectrometry analysis and various nuclear magnetic resonance spectroscopic methods. The protective effect of SG-168 in PC12 cells with H(2)O(2)-induced oxidative damage was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. As expected, incubation with H(2)O(2) for 2 hours resulted in cell viability of 31.8% compared to the control, while pretreatment of SG-168 increased cell viability by 15-50% compared to the H(2)O(2)-stressed control cells. These results showed that SG-168 inhibits H(2)O(2)-induced apoptotic cell death. Interestingly, flow cytometric analysis showed that H(2)O(2)-treated PC12 cells incubated with SG-168 exhibited greatly suppressed apoptosis. In summation, the results of this study suggest that SG-168 has potential as a new antioxidant agent against neuronal diseases.
    Journal of medicinal food 01/2011; 14(1-2):120-7. · 1.39 Impact Factor
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    ABSTRACT: 4,8-Dihydroxy-5-methoxy-2-naphthaldehyde (Compound I) was isolated from blackened heartwood of Diospyros kaki and was methylated with diazomethane. Antioxidant and cytotoxic activities of Compound I and two methylated derivatives [4-hydroxy-5,8-dimethoxy-2-(2-oxopropyl)-naphthalene (D-1) and 2-glycidyl-4-hydroxy-5,8-dimethoxy naphthalene (D-2)] were evaluated. Compound I showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and reducing power than D-1 and D-2. However, D-1 and D-2 exhibited slightly stronger 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)+ (ABTS+) radical scavenging activity than Compound I. Compound I also exhibited stronger cytotoxic activity than D-1 and D-2 against the growth of HT-29 colon cancer cells. The results supported the hypothesis that methylation of naphthalene derivatives slightly increased ABTS+ radical scavenging activity, but significantly decreased DPPH radical scavenging activity, reducing power, and cytotoxic activity. Key wordsNaphthalene derivatives–Persimmon wood–Antioxidant activity–Cytotoxic activity
    Journal of Wood Science 01/2011; 57(2):161-165. · 0.77 Impact Factor
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    ABSTRACT: This study was performed to assess the neuroprotective effects of methanolic extracts from sweet persimmon peel (PPE) against glutamate-induced cytotoxicity in hybridoma N18-RE-105 cells. The neuroprotective effects of PPE in N18-RE-105 cells were measured using the MTT reduction assay, LDH release assay, and phase-contrast microscopy. The results of the MTT reduction assay showed that treating cells with 500 PPE resulted in cell viability of 66.9%. Additionally, the morphological changes and the results of the LDH release assay showed that glutamate-induced damage to nerve cells was strongly inhibited by PPE. GSH content of N18-RE-105 cells was 3.5 compared to that of the control, whereas pretreatment with 500 PPE increased GSH content by 4.7 . PPE was fractionated with hexane, and that layer had the highest neuroprotective effects in glutamate-stressed N18-RE-105 cells. In conclusion, our data showed that glutamate potentiated the effects of N18-RE-105 cell death by a mechanism involving oxidative stress. Therefore, PPE may be a potential candidate for prevention and therapy of neurodegenerative diseases.
    Korean journal of food and cookery science. 01/2011; 27(4).
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    Sang-Bong Lee, Hae-Ryong Park
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    ABSTRACT: Natural products have recently become the focus of increased research interest due to their potential pharmacological activities. Therefore, we established a program to screen natural products for cytotoxic activity using the MTT reduction assay system to test HT-29 human colon cancer cells. During the course of screening, we found that the acetone extracts of guava (Psidium guajava L.) branch (GBA) had cytotoxic effects on HT-29 cells. The GBA showed highly cytotoxic effects via the MTT reduction assay, LDH release assay, and colony formation assay. In particular, the GBA of the 250 µ µ µ µg/ml showed 35.5% inhibition against growth of HT-29 cells. As expected, GBA induced characteristic apoptotic effects in HT-29 cells, including chromatin condensation and sharking that occurred 24 h after the cells had been treated at a concentration level of 250 µ µ µ µg/ml. To examine the functions on apoptosis, we used a flow cytometric analysis. The apoptotic cells were distributed according to the cell cycle phase shown by sub-G1 DNA content.
    Journal of Medicinal Plants Research. 04/2010; 4:891-896.
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    ABSTRACT: Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor-specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose-deprived conditions. Here we identify arctigenin (ARC-G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC-G blocked expression of UPR target genes such as phosphorylated-PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2 alpha during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase-9 and -3. Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors.
    Journal of Cellular Physiology 03/2010; 224(1):33-40. · 4.22 Impact Factor
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    ABSTRACT: Oyster mushroom is a popular edible mushroom which has various colorful fruit bodies. The objective of this study was to determine the antioxidant and the anticancer activities of oyster mushrooms (OM) with different colors such as dark-grey strain (Pleurotus ostreatus), yellow strain (Pleurotus cornucopiae), and pink strain (Pleurotus salmoneostramineus). The methanolic extracts from OMs were prepared for this study. Among these OMs, the extract from the yellow strain showed the highest radical scavenging activity, reducing power, ferrous chelating ability, and total phenolic contents. Radical scavenging activity of yellow strain was about 3 times higher than that of dark-grey strain. On the other hand, the extracts of dark-grey and pink strains showed higher suppressive effect against growth of human colon cancer cell line HT-29 with survival rates of 39.9 and 40.7%, respectively, than that of yellow strain. These results showed that the antioxidant and the anticancer activities of OMs varied by the colors of fruit bodies.
    Journal of Medicinal Plants Research. 01/2010; 3:1016-1020.
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    01/2010;
  • Journal of the Korean Society of Food Science and Nutrition 01/2010; 39(4):500-505.
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 33(49).
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    ABSTRACT: The oxidative stress induced by reactive oxygen species (ROS) may play an important role in the pathogenesis of neurodegenerative diseases. In this study, we investigated the neuroprotective effects of methanolic extracts of Prunella Spica (PSE) against -induced oxidative stress in PC12 cells. The cells exposed to -induced oxidative stress were treated with various concentrations of PSE; this treatment resulted in the induction of a dose-dependent protective effect, which was evidenced by the results of MTT reduction assay, lactate dehydrogenase (LDH) release assay, morphological assay, and colony-formation assay. Interestingly, we also observed reduction of apoptotic bodies in the Hoechst staining and flow cytometric analysis. These data show that apoptosis was significantly suppressed in the PC12 cells that were exposed to -induced oxidative stress and treated with PSE. These results suggest that Prunella Spica could be a new potential protective agent against -induced oxidative stress.
    Journal of Life Science. 01/2010; 20(7).
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    ABSTRACT: The neuroprotective effects of extracts from various parts of peanut sprouts on glutamate-induced neurotoxicity in N18-RE-105 cells were investigated. This study was performed to evaluate the neuroprotective activity of methanolic extracts from the whole (WME), heads (HME), and stems (SME) of peanut sprouts. The neuroprotective effects of these extracts were measured by MTT reduction assay, LDH release assay, phase-contrast microscopy, and flow cytometric analysis on the N18-RE-105 cells. Among these extracts, the HME showed the greatest neuroprotective effects, and was further fractionated with hexane, diethyl ether, ethyl acetate, and water, according to degree of polarity. Out of the fractionated extracts, the diethyl ether layer showed the highest activity on glutamate-induced cytotoxicity in N18-RE-105 cells. The sub-G1 DNA contents of the glutamate-induced severely apoptotic N18-RE-105s were measured by flow cytometric analysis to confirm the HME's anti-apoptotic activity. Interestingly, after incubation with 100 mg/ml of the HME, the proportion of sub-G1 cells of the glutamate-stressed N18-RE-105s had been greatly reduced, from 58.5% to 9.1%. These results imply that HME may have strong potential as a chemotherapeutic agent against neuronal diseases.
    Journal of Life Science. 01/2010; 20(2).
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    ABSTRACT: Pancreatic cancer cells are sometimes exposed to stressful microenvironments such as glucose deprivation, hypoxia, and starvation of other nutrients. These stresses, which are characteristic of poorly vascularized solid tumors, activate the unfolded protein response (UPR). The UPR is a stress-signaling pathway present in tumor cells that is associated with molecular chaperone GRP78. Induction of GRP78 has been found to increase cell survival and decrease apoptotic potential through genetic alterations. Thus GRP78 may represent a novel target in the development of anticancer drugs. Here we established a novel screening program to identify chaperone modulators that exhibit preferential cytotoxic activity in glucose-deprived pancreatic cancer cells. During the course of our screening, we isolated an active substance, Ponciri Fructus (PF), from an herbal medicine source and identified it as a down-regulator of GRP78. As expected, PF inhibited expression of the GRP78 protein under glucose-deprivation conditions in a dose-dependent manner. Furthermore, it induced selective cytotoxicity against glucose-deprived cancer cells; this effect was not observed under normal growth conditions. We also detected apoptotic bodies on Hoechst staining and attempted to determine whether PF-induced apoptosis involved caspase-3 activation. Our results suggest that the GRP78-inhibitory action of PF was dependent on strict hypoglycemic conditions and that it resulted in the selective death of glucose-deprived pancreatic cancer cells.
    Bioscience Biotechnology and Biochemistry 10/2009; 73(10):2167-71. · 1.27 Impact Factor
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    ABSTRACT: Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of the UPR is the transcription program activation, which allows the cell to survive under stress conditions. Here, we show that the UPR transcription program is disrupted by the antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production of the UPR transcription activators XBP1 and ATF4 and induce massive cell death during glucose deprivation as did the antitumor macrocyclic compound versipelostatin. Gene expression profiling shows remarkable similarity in the modes of action of biguanides and versipelostatin determined by the broad range of glucose deprivation-inducible genes. Importantly, during glucose deprivation, most of the biguanide suppression genes overlap with the genes induced by tunicamycin, a chemical UPR inducer. Gene expression profiling also identifies drug-driven signatures as a tool for discovering pharmacologic UPR modulators. Our findings show that disrupting the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical genomic basis for developing UPR-targeting drugs against solid tumors.
    Cancer Research 06/2009; 69(10):4225-34. · 9.28 Impact Factor
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    ABSTRACT: This study evaluated the neuroprotective effect of extracts from the root bark of Morus alba (MA) against glutamate-induced cytotoxicity in neuronal cells. Glutamate-induced cytotoxicity was shown by MTT reduction assay. The neuroprotective effects of methanol, ethanol, and acetone extracts from MA against glutamate-induced cytotoxicity were measured. Among the three extracts, the methanolic extracts showed the highest protective effect, as determined by the results of an morphological assay, a lactate dehydrogenase release assay. Furthermore, the methanol extracts were fractionated sequentially with hexane, diethyl ether, ethyl acetate, and water layer according to degree of polarity. The hexane fractions exhibited a neuroprotective effect against glutamate-stressed N18-RE-105 cells. Therefore, these results suggest that extracts of MA could be a new potential candidate as a protective substance against glutamate-induced cytotoxicity.
    Journal of Life Science. 01/2009; 19(7).
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    ABSTRACT: We recently isolated a macrocyclic compound, versipelostatin (VST), that exerts in vivo antitumor activity. VST shows unique, selective cytotoxicity to glucose-deprived tumor cells by preventing the unfolded protein response (UPR). Here we show that eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), a negative regulator of eukaryotic initiation factor 4E-mediated protein translation, plays a role in the UPR-inhibitory action of VST. Indeed, 4E-BP1 is aberrantly activated by VST. This activation occurs specifically during glucose deprivation and results in profound translation repression and prevents induction of the typical UPR markers glucose-regulated protein (GRP) 78 and activating transcription factor (ATF) 4. Our overexpression and knockdown experiments showed that 4E-BP1 can regulate GRP78 and ATF4 expression. These mechanisms appear to be specific for VST. By contrast, rapamycin, which activates 4E-BP1 regardless of cellular glucose availability, has only marginal effects on the expression of GRP78 and ATF4. Our present findings demonstrate that aberrant 4E-BP1 activation can contribute to UPR preventing by VST, possibly through a mechanism that does not operate in rapamycin-treated cells.
    Cancer Science 01/2009; 100(2):327-33. · 3.48 Impact Factor
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    ABSTRACT: The Cosmos bipinnatus has been used in a traditional herbal remedy for various diseases such as jaundice, intermittent fever, and splenomegaly. The present study describes the preliminary evaluation of antioxidant activities and antigenotoxic effect of Cosmos bipinnatus flowers according to four different colors (white, pink, orange, and violet). The antioxidants properties were evaluated by determining TPC, DPPH RSA, ABTS RSA, and RP. The highest TPC of methanolic CFE (at concentration of 1 mg/ml) showed in violet colored CF (1,013 microM), and IC(50) of DPPH RSA, ABTS RSA, and RP were also the lowest in violet colored CFE with values of 0.61, 1.48, and 0.82 mg/ml, respectively. The antigenotoxic effect of the CFE on DNA damage induced by H(2)O(2) in human leukocytes was evaluated by Comet assay. Pretreatments with CFE produced significant reductions in oxidative DNA damage at the concentration of 500 microg/ml, except for violet colored CFE. The ED(50) value of white colored CFE has shown the highest inhibition (0.40 mg/ml) on H(2)O(2) induced DNA damage, followed by orange > pink > violet color. These results suggested that Cosmos bipinnatus has significant antioxidant activity and protective effect against oxidative DNA damage.
    Plant Foods for Human Nutrition 09/2008; 63(4):205-10. · 2.36 Impact Factor

Publication Stats

531 Citations
85.53 Total Impact Points

Institutions

  • 2009–2012
    • Japanese Foundation for Cancer Research
      Edo, Tōkyō, Japan
  • 2005–2012
    • Kyungnam University
      Changnyeong, South Gyeongsang, South Korea
  • 2002–2010
    • The University of Tokyo
      • Institute of Molecular and Cellular Biosciences
      Edo, Tōkyō, Japan
  • 2008
    • Ewha Womans University
      • Department of Life Sciences
      Seoul, Seoul, South Korea
  • 2003–2007
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • Biological Resource Center
      Anzan, Gyeonggi Province, South Korea