Faculty Profiles - KIM Hye-Sook

Papers - KIM Hye-Sook

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抗マラリア薬として開発中の化合物に見出された強力な抗HCV活性(Potent anti-HCV activities found in preclinical anti-malarial drugs)

上田優輝, 森京子, 団迫浩方, 金惠淑, 綿矢有佑, 池田正徳, 加藤宣之

日本癌学会総会記事 71回 116 - 116 2012.8

Andirolides H-P from the flower of andiroba (Carapa guianensis, Meliaceae) Reviewed

Yuji Tanaka, Asami Sakamoto, Takanobu Inoue, Takeshi Yamada, Takashi Kikuchi, Tetsuya Kajimoto, Osamu Muraoka, Akira Sato, Yusuke Wataya, Hye Sook Kim, Reiko Tanaka

Tetrahedron 68 ( 18 ) 3669 - 3677 2012.5

Three new gedunins, an andirobin, three mexicanolides, and two phragmalin-type limonoids named andirolides H (1), I (2), J (3), K (4), L (5), M (6), N (7), O (8), and P (9) were isolated from an oil of the flower of Carapa guianensis Aublet (Meliaceae). Their structures including the absolute configurations were determined by means of the NMR and CD spectra as well as FABMS. Andirolide H (1) showed antimalarial activity against Plasmodium falciparum in vitro. © 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.tet.2011.12.076

Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives Reviewed

Akira Sato, Satoru Kawai, Akiko Hiramoto, Masayuki Morita, Natsuki Tanigawa, Yukari Nakase, Yuka Komichi, Masahiro Matsumoto, Osamu Hiraoka, Kazuyuki Hiramoto, Hidekazu Tokuhara, Araki Masuyama, Masatomo Nojima, Kazutaka Higaki, Hikoya Hayatsu, Yusuke Wataya, Hye-Sook Kim

PARASITOLOGY INTERNATIONAL 60 ( 4 ) 488 - 492 2011.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-l-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cyclic peroxides having carboxyl functionality was prepared based on the antimalarial candidate, N-251, and their antimalarial activities were determined. The reactions of N-89 and its derivatives with Fe(II) demonstrated a highly efficient formation of the corresponding carbon radical which may be suspected as a key for the antiparasitic activity. Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.parint.2011.08.017

Schistosomicidal and antifecuridity effects of oral treatment of synthetic endoperoxide N-89 Reviewed

Toshie Taniguchi, Takashi Kumagai, Rieko Shimogawara, Shizuko Ichinose, Akiko Hiramoto, Akira Sato, Masayuki Morita, Masatomo Nojima, Hye-Sook Kim, Yusuke Wataya, Nobuo Ohta

PARASITOLOGY INTERNATIONAL 60 ( 3 ) 231 - 236 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

1,2,6,7-Tetraoxaspiro[7.11]nonadecane (N-89) is a chemically synthesized compound with good efficacy against malaria parasites. We observed strong anti-schistosomal activities of N-89 both in vitro and in vivo. In a murine model with experimental infection of Schistosoma mansoni, orally administered N-89 at the dose of 300 mg/kg resulted in a significant reduction in worm burden (63%) when mice were treated at 2-weeks postinfection. Strong larvicidal effects of N-89 were confirmed in vitro; schistosomula of S. mansoni were killed by N-89 at an EC50 of 16 nM. In contrast, no significant reduction in worm burden was observed when N-89 was administered at 5 weeks postinfection in vivo. However, egg production was markedly suppressed by N-89 treatment at that time point. On microscopic observation, the intestine of N-89-treated female worms seemed to be empty compared with the control group, and the mean body length was significantly shorter than that of controls. Nutritional impairment in the parasite due to N-89 treatment was possible, and therefore quantification of hemozoin was compared between parasites with or without N-89 treatment. We found that the hemozoin content was significantly reduced in N-89 treated parasites compared with controls (P<0.001). The surface of adult worms was observed by scanning and transmission electron microscopy, but there were no apparent changes. Taken together, these observations suggested that N-89 has strong antischistosomal effects, probably through a unique mode of drug efficacy. As N-89 is less toxic to mammalian host animals, it is a possible drug candidate against schistosomiasis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.parint.2011.02.007

Antimalarial activity of endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol Reviewed

Akira Sato, Akiko Hiramoto, Masayuki Morita, Masahiro Matsumoto, Yuka Komich, Yukari Nakase, Natsuki Tanigawa, Osamu Hiraoka, Kazuyuki Hiramoto, Hikoya Hayatsu, Kazutaka Higaki, Satoru Kawai, Araki Masuyama, Masatomo Nojima, Yusuke Wataya, Hye-Sook Kim

PARASITOLOGY INTERNATIONAL 60 ( 3 ) 270 - 273 2011.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. Here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against P. falciparum and Plasmodium berghei parasites. The N-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (EC(50) 2.3 X 10(-8) M; ED(50) 15 mg/kg (per oral)). The potencies were similar to that of artemisinin in vitro and greater than artemisinin's activity in vivo (p.o.). In addition, N-251 has little toxicity: a single oral administration at 2000 mg/kg to a rat gave no health problems to it. Administration of N-251 to mice bearing 1% of parasitemia (per oral 68 mg/kg, 3 times a day for 3 consecutive days) resulted in a dramatic decrease in the parasitemia: all the 5 mice given N-251 were cured without any recurrence, with no diarrhea or weight loss occurring in the 60 days of experiment. N-251 deserves more extensive clinical evaluation, desirably including future trials in the human. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.parint.2011.04.001

Association of RNase L with a Ras GTPase-activating-like protein IQGAP1 in mediating the apoptosis of a human cancer cell-line Reviewed

Akira Sato, Tomoharu Naito, Akiko Hiramoto, Kazato Goda, Takuya Omi, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

FEBS Journal 277 4464 - 4473 2010.11

Mammalian intracellular ribonuclease L (RNase L) is a latent endoribonuclease that functions against viral infections as an apoptosis-inducing protein, and its activity requires intracellular 5′-end-triphosphorylated-2′,5′ oligoadenylates (2-5A) as an activator. Previously, we showed that RNase L can be activated in human cancer cell line HT1080 by an RNA polymerase I inhibitor, 1-(3-C-ethynyl-β-D-ribo- pentofuranosyl)cytosine (3′-ethynylcytidine; ECyd). In ECyd-treated cells, knockdown of the RNase L resulted in a marked decrease in c-jun N-terminal kinase (JNK) phosphorylation, thereby inhibiting apoptosis. We investigate RNase L binding partners by focused proteomic approach using immunoprecipitation with anti-RNase L IgG and mass spectrometry. We found that the IQ motif-containing Ras GTPase-activating-like protein 1 (IQGAP1) can associate with RNase L, and that phosphorylation occurs on the IQGAP1. ECyd-induced JNK phosphorylation and apoptosis were inhibited when IQGAP1 was knocked down with a small interfering RNA. These results raise the interesting possibility that the RNase L-IQGAP1 association may regulate JNK phosphorylation in RNase L-madiated apoptosis. It is likely IQGAP1 works as a regulator in apoptosis.© 2010 The Authors Journal compilation © 2010 FEBS.

DOI： 10.1111/j.1742-4658.2010.07833.x

GERANYL DERIVATIVES OF ISOQUINOLINE ALKALOIDS SHOW INCREASED BIOLOGICAL ACTIVITIES Reviewed

Yumi Nishiyama, Kinuko Iwasa, Suguru Okada, Sousuke Takeuchi, Masataka Moriyasu, Miyoko Kamigauchi, Junko Koyama, Atsuko Takeuchi, Harukuni Tokuda, Hye-Sook Kim, Yusuke Wataya, Kazuyoshi Takeda, Yi-Nan Liu, Pei-Chi Wu, Kenneth F. Bastow, Toshiyuki Akiyama, Kuo-Hsiung Lee

HETEROCYCLES 81 ( 5 ) 1193 - 1229 2010.5

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Three types of isoquinoline alkaloids were tested for antimicrobial, cytotoxic, anti-malarial, anti-oxidant, and anti-HIV activities, as well as inhibitory activity against Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. N- or O-Geranylation contributed to increased potency in four types of activities except anti-HIV and anti-oxidant. Some types of alkaloids may be useful as lead compounds for developing potential chemotherapeutic agents. N,N-Geranylated salsolinol was significantly active in three different assays, antimicrobial, cytotoxic, and EBV-EA, and may be a most useful compound.

DOI： 10.3987/COM-10-11912

Protein Expression Profiles of Necrosis and Apoptosis Induced by 5-Fluoro-2 '-deoxyuridine in Mouse Cancer Cells Reviewed

Akira Sato, Akito Satake, Akiko Hiramoto, Yusuke Wataya, Hye-Sook Kim

JOURNAL OF PROTEOME RESEARCH 9 ( 5 ) 2329 - 2338 2010.5

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER CHEMICAL SOC

We have investigated the molecular mechanisms regulating the necrosis and apoptosis that occur on treatment of mouse mammary tumor FM3A cells with 5-fluoro-2'-deoxyuridine (FUdR), a potent anticancer agent, using the original clone F28-7 and its variant F28-7-A cells. Previously, we reported an interesting observation that FUdR induces a necrotic morphology in F28-7 but an apoptotic morphology in F28-7-A cells. We have now analyzed the protein expression profiles of these FUdR-induced necrosis and apoptosis. Thus, proteome analysis of these clones by two-dimensional gel electrophoresis and mass spectrometry showed that the cytoplasmic intermediate filament protein, cytokeratin-19, is expressed at a significantly higher level in F28-7 than in F28-7-A cells. This strong expression was detected both in untreated and FUdR-treated stages of F28-7 cells. We interpreted this phenomenon as suggesting that cytokeratin-19 possesses a function in leading the cell to apoptosis. We performed a knockdown of cytokeratin-19 expression in F28-7 cells by use of the small interfering RNA technique. Indeed, a lowering of the cytokeratin-19 expression down to the level in F28-7-A occurred, and the FUdR-induced death morphology of this knockdown F28-7 was apoptosis, instead of the necrosis usually observable in the FUdR-treated F28-7. It is known that the cytoskeletal protein cytokeratin-19 undergoes caspase-mediated degradation during apoptosis. Our present finding provides an interesting possibility that cytokeratin-19 may have a key role in regulating cell-death morphology.

DOI： 10.1021/pr9010537

Selective accumulation of rhodacyanine in plasmodial mitochondria is related to the growth inhibition of malaria parasites Reviewed

D. Morisaki, H.-S. Kim, H. Inoue, H. Terauchi, S. Kuge, A. Naganuma, Y. Wataya, H. Tokuyama, M. Ihara, K. Takasu

Chemical Science 1 ( 2 ) 206 - 209 2010

Antimalarial artemisinin and tetraoxane endoperoxides behave differently in the oxidative degradation of unsaturated phospholipid Reviewed

Naokazu Kumura, Hirotaka Furukawa, Arnold N. Onyango, Minoru Izumi, Shuhei Nakajima, Hideyuki Ito, Tsutomu Hatano, Hye-Sook Kim, Yusuke Wataya, Naomichi Baba

CHEMISTRY AND PHYSICS OF LIPIDS 160 S28 - S29 2009.8

Role of RNase L in apoptosis induced by 1-(3-C-ethynyl-β-d-ribo- pentofuranosyl)cytosine Reviewed

Tomoharu Naito, Tatsushi Yokogawa, Satoshi Takatori, Kazato Goda, Akiko Hiramoto, Akira Sato, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Yusuke Wataya, Hye Sook Kim

Cancer Chemotherapy and Pharmacology 63 837 - 850 2009.4

Purpose: 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)cytosine (ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. The present studies have been performed to elucidate the overall mechanisms of ECyd-induced apoptotic cell death. Methods: Cultured cells of mouse mammary carcinoma FM3A and human fibrosarcoma HT 1080 lines were used. The efficacy of RNA synthesis inhibition by ECyd was assessed by kinetic analysis using nuclei isolated from FM3A cells. RNA status in ECyd-treated cells was investigated by Northern blots, and the cleavage sites of RNA were identified by rapid amplification of 5′ cDNA ends (5′-RACE). The effect of protein functions on the ECyd-induced apoptotic pathway was analyzed by siRNA and immunohistochemical techniques. Apoptotic cells were detected by TdT-mediated dUTP-biotin Nick End Labeling (TUNEL) assay. Results: ECyd induces inhibition of RNA synthesis in vitro and in vivo, which appears to be a major cause for the apoptosis. It is known that ECyd is converted inside the cell into its 5′-triphosphate (ECTP). We have now found in test-tube experiments that ECTP strongly inhibits the activity of RNA polymerase I by competing with CTP. In the absence of robust RNA synthesis, the cellular RNAs would be destined to break down. RNase L was found to be playing a role in the breakdown: thus, the 28S rRNA-fragmentation pattern observed for the ECyd-treated cells was very similar to that observable in an in vitro treatment of the 28S ribosomes with RNase L. Association of RNase L with the cytotoxic action of ECyd was confirmed by use of the siRNA-mediated suppression of the cellular RNase L. Thus, the cells in which the RNase L was knocked-down were highly resistant to the cytotoxic action of ECyd. Further events, downstream of the RNase L action that can lead to the eventual apoptosis, would conceivably involve the phosphorylation of c-jun N-terminal kinase and subsequent decrease in mitochondrial membrane-potential. Evidence to support this flow of events was obtained by siRNA-experiments. Conclusion: The results from this study demonstrated that RNase L is activated after the inhibition of RNA polymerase, and induces mitochondria-dependent apoptotic pathway. We propose this new role for RNase L in the apoptotic mechanism. These findings may open up the possibility of finding new targets for anticancer agents. © 2008 Springer-Verlag.

DOI： 10.1007/s00280-008-0810-y

Toxoplasma gondii: A simple high-throughput assay for drug screening in vitro Reviewed

ChunMei Jin, Kusuma Kaewintajuk, JingHua Jiang, WooJin Jeong, Masaki Kamata, Hye-Sook Kim, Yusuke Wataya, Hyun Park

EXPERIMENTAL PARASITOLOGY 121 ( 2 ) 132 - 136 2009.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

Toxoplasma gondii is the etiologic agent of toxoplasmosis. Although the combination of sulfadiazine and pyrimethamine is used as therapy for this disease, these drugs can have serious side effects and its use is limited in pregnancy. Therefore there is a need for new anti-T gondii drugs in the clinic. Some systems for T. gondii drug screening have been described, but these have limitations and can be difficult. In order to solve these problems, we established a system to screen drugs in vitro that involved using cell viability methods to calculate drug selectivities, which are Trypan blue, [3-(4,5-dimethylthiazol-zyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazoliuzolium, inner salt] (MTS) method and lactate dehydrogenase (LDH) assay. These assays were simple to establish and perform. The IC(50) values calculated from the morphological assay were not significantly different from the EC(50) values calculated using the other three methods. In particular, the results of the morphological assay showed a distinct association with the MTS assay (R = 0.9841). These assays could be used for a wide range of applications in the screening of new drugs and may provide an alternative to the techniques currently used to screen for candidate anti-T. gondii compounds in vitro. In this study, we also tested many compounds and identified some that had a good anti-T gondii effect in vitro based on the MTS assay. This simple and fast system allowed us to determine which compounds to investigate further using in vivo experiments. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.exppara.2008.10.006

Synthesis of Novel Conjugates of Tetraoxane Endoperoxide with Bis (Quaternary Ammonium Salts)

KUMURA Naokazu, FURUKAWA Hirotaka, KOBAYASHI Michiyo, ONYANGO Arnold N., IZUMI Minoru, NAKAJIMA Shuhei, KIM Hye-Sook, WATAYA Yusuke, BABA Naomichi

Agricultural and Biological Chemistry 73 ( 1 ) 217 - 220 2009

Language：English Publisher：Japan Society for Bioscience, Biotechnology, and Agrochemistry

Novel water-soluble conjugates of 1,2,4,5-tetraoxane bis(quaternary ammonium salts) were synthesized in a relatively stable crystalline form via four steps starting from methyltrioxorhenium-catalyzed endo-peroxidation of ethyl 4-oxocyclohexanecarboxylate with hydrogen peroxide in hexafluoro-2-propanol. The assay for the in vitro toxicity of water-soluble tetraoxanes 5a–5d to malaria parasites indicate that they were inactive against the Plasmodium falciparum FCR-3 strain.

DOI： 10.1271/bbb.80571

Other Link： https://jlc.jst.go.jp/DN/JALC/00324722978?from=CiNii

Different behavior of artemisinin and tetraoxane in the oxidative degradation of phospholipid

Kumura, N, Furukawa, H, Onyango, A.N, Izumi, M, Nakajima, S, Ito, H, Hatano, T, Kim, H.-S, Wataya, Y, Baba, N

Chemistry and Physics of Lipids 160 ( 2 ) 114 - 120 2009

Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3 '-termini

Yoshihito Ueno, Koshi Kawada, Tomoharu Naito, Aya Shibata, Kayo Yoshikawa, Hye-Sook Kim, Yusuke Wataya, Yukio Kitade

BIOORGANIC & MEDICINAL CHEMISTRY 16 ( 16 ) 7698 - 7704 2008.8

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Short-interfering RNAs (siRNAs) conjugated with lipophilic groups at their 3'-termini were synthesized. The properties of the synthesized siRNAs were examined in detail, and it was found that at low concentrations, their silencing abilities were dependent on the positions of the modi. cations and the types of organic molecules attached. Although the modi. cation of siRNAs with palmitic acid or oleic acid at the 3'-end slightly reduced their silencing activities, siRNAs had enough abilities to induce RNAi at 10 nM concentrations. On the other hand, the modi. cation of siRNAs with cholesterol at the 3'-end of the passenger strand was tolerated; however, the modi. cation at the guide strand significantly reduces its silencing activity. The siRNAs modified with the lipophilic groups did not possess ability to penetrate the plasma membranes of HT-1080 cells without the transfection reagent. However, the results described in this report will aid in designing novel siRNAs with cell membrane-permeable molecules. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.bmc.2008.07.010

Gene expression profiles of necrosis and apoptosis induced by 5-fluoro-2 '-deoxyuridine

Akira Sato, Akiko Hiramoto, Yusuke Uchikubo, Eriko Miyazaki, Akito Satake, Tomoharu Naito, Osamu Hiraoka, Tsuyoshi Miyake, Hye-Sook Kim, Yusuke Wataya

GENOMICS 92 ( 1 ) 9 - 17 2008.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE

5-Fluoro-2'-deoxyuridine (FUdR), a potent anticancer agent, exerts its effects by inhibiting thymidylate synthase, an essential machinery for DNA synthesis in cell proliferation. Also, cell death is caused by FUdR, primarily due to an imbalance in the nucleotide pool resulting from this enzyme inhibition. We have investigated the cancer cell death induced by FUdR, focusing on its molecular mechanisms. Using mouse mammary tumor FM3A cell lines, the original clone F28-7 and its variant F28-7-A cells, we previously reported an interesting observation that FUdR induces a necrotic morphology in F28-7, but induces, in contrast, an apoptotic morphology in F28-7-A cells. In the present study, to understand the molecular mechanisms underlying these differential cell deaths, i.e., necrosis and apoptosis, we investigated the gene expression changes occurring in these processes. Using the cDNA microarray technology, we found 215 genes being expressed differentially in the necrosis and apoptosis. Further analysis revealed differences between these cell lines in terms of the expressions of both a cluster of heat shock protein (HSP)-related genes and a cluster of apoptosis-related genes. Notably, inhibition of HSP90 in F28-7 cells caused a shift from the FUdR-induced necrosis into apoptosis. These findings are expected to lead to a better understanding of this anticancer drug FUdR for its molecular mechanisms and also of the general biological issue, necrosis and apoptosis. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygeno.2008.02.002

Detection of malaria parasites in mosquitoes from the malaria-endemic area of Chakaria, Bangladesh

Akter Tangin, Yuka Komichi, Yukiko Wagatsuma, Haque Rashidul, Yusuke Wataya, Hye-Sook Kim

BIOLOGICAL & PHARMACEUTICAL BULLETIN 31 ( 4 ) 703 - 708 2008.4

Language：English Publishing type：Research paper (scientific journal) Publisher：PHARMACEUTICAL SOC JAPAN

Malaria is one of the major public health problems of Bangladesh. We investigated the mosquito populations infected with malaria parasites in a malaria-endemic area Chakaria, Bangladesh, where Anopheles dirus and Anopheles minimus are the principal vectors. Anopheles mosquitoes were collected with a CDC miniature light trap from inside households in June 2007. A total of 868 mosquitoes were collected, among which females numbered 669 (77.1%). The species of female Anopheles mosquitoes were identified morphologically, and 651 were A. minimus and the remaining 18 were other Anopheles species. Malaria parasite DNA from individual female mosquitoes was extracted and distinguished using the microtiter plate hybridization (MPH) technique targeting the 18S rRNA of human malaria parasites. Nineteen mosquitoes were malaria parasite positive: 12 for Plasmodium falciparum, 1 for Plasmodium vivax, and 6 for both R falciparum and P vivax. This is the first time that the MPH technique was used for distinguishing malaria parasites in mosquitoes and the first report from Chakaria. Our results may contribute to planning and assessing malaria control strategies in Chakaria.

DOI： 10.1248/bpb.31.703

Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2 '-deoxyuridine

Akira Sato, Akiko Hiramoto, Akito Satake, Eriko Miyazaki, Tomoharu Naito, Yusuke Wataya, Hye-Sook Kim

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 27 ( 5 ) 433 - 438 2008

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS INC

We report that anticancer 5-fluoro-2'-deoxyuridine (FUdR) shows cytotoxicity against mouse cancer cell line FM3A, using a progeny clone F28-7 and its variant F28-7-A. In this process, the cell-death morphology is different between F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A cells. In the proteomic analysis of these cells before their exposure to FUdR, the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in F28-7-A, suggesting that lamin B1 may possess a function to regulate the morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells was performed by use of the small interfering RNA technique, resulting in a decrease of the lamin B1-expression level down to the level in F28-7-A. Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was apoptosis, definitely different from the necrosis that occurs in the FUdR-treated original F28-7. Thus, the swelling feature for the necrosis was no longer observable, and instead cell shrinkage typical of apoptosis took place in almost all the cells examined. This finding suggests a new role for lamin B1 as a regulator in cell death.

DOI： 10.1080/15257770802086864

In vitro antimalarial activity of flavonoids and chalcones

Soon Sung Lim, Hye-Sook Kim, Dong-Ung Lee

BULLETIN OF THE KOREAN CHEMICAL SOCIETY 28 ( 12 ) 2495 - 2497 2007.12

Preparation of quinoline hexose analogs as novel chloroquine-resistant malaria treatments (1). Synthesis of 4-hydroxyquinoline-beta-glucosides

Hiroshi Suzuki, Nagwa S. M. Aly, Yusuke Wataya, Hye-Sook Kim, Ikumi Tamai, Masaki Kita, Daisuke Uemura

CHEMICAL & PHARMACEUTICAL BULLETIN 55 ( 5 ) 821 - 824 2007.5

Language：English Publishing type：Research paper (scientific journal) Publisher：PHARMACEUTICAL SOC JAPAN

Quinoline hexose analogs are expected to be useful as novel agents for treatment of chloroquine-resistant malaria. Here, we report preparation of 4-hydroxy quinoline-beta-glucosides from anilines in 4 steps.

DOI： 10.1248/cpb.55.821

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