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2008 Fiscal Year Final Research Report

Research on a selection reference of chemopreventive agents for cancer and a development of tailor-made medicine for cancer prevention

Research Project

  • PDF
Project/Area Number 17209022
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SAKAI Toshiyuki  Kyoto Prefectural University of Medicine, 医学研究科, 教授 (20186993)

Co-Investigator(Kenkyū-buntansha) SOWA Yoshihiro  京都府立医科大学, 医学研究科, 准教授 (70315935)
MATSUZAKI Yoichiro  京都府立医科大学, 医学研究科, 助手 (70282522)
YOSHIDA Tatsushi  京都府立医科大学, 医学研究科, 助教 (80315936)
YOGOSAWA Shingo  京都府立医科大学, 医学研究科, 助教 (70381936)
HORINAKA Mano  京都府立医科大学, 医学研究科, 助教 (80512037)
Project Period (FY) 2005 – 2008
Keywords癌 / 癌抑制遺伝子 / テーラーメイド予防 / p53 / RB / DR5 / TRAIL / p16
Research Abstract

ヒト発癌において最も重要な癌抑制遺伝子p53は、多くの癌で失活している。本研究では、実際的な癌予防を目指し、約800種類の食品由来成分や薬剤を用いてその機能を回復・活性化させる物質の探索を行い、その作用機構を解析した。その結果、ヒト癌細胞に対して細胞増殖抑制効果を有する物質を複数見出した。さらに、その作用機構がp53標的遺伝子の発現量の調節であることを明らかにした。現在、それらを組み合わせ、動物試験により発癌抑制における相乗・相加効果の検討に移った段階である。

  • Research Products

    (63 results)

All 2009 2008 2007 2006 2005 Other

All Journal Article (47 results) (of which Peer Reviewed: 47 results) Presentation (14 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Insight into estrogenicity of phytoestrogens using in silico simulation2009

    • Author(s)
      Sugiyama H, Sowa Y(他6名)
    • Journal Title

      Biochem Biophys Res Commun 379

      Pages: 139-44

    • Peer Reviewed
  • [Journal Article] Death receptor 5 targeting activity-guided isolation of isoflavones from Millettia brandisiana and Ardisia colorata and evaluation of ability to induce TRAIL-mediated apoptosis2009

    • Author(s)
      Kikuchi H, Sakai T(他4名)
    • Journal Title

      Bioorg Med Chem 17

      Pages: 1181-6

    • Peer Reviewed
  • [Journal Article] Nitric oxide sensitizes tumor cells to TRAIL-induced apoptosis via inhibition of the DR5 transcription repressor Yin Yang 12009

    • Author(s)
      Huerta-Yepez S, Sakai T(他5名)
    • Journal Title

      Nitric Oxide. 20

      Pages: 39-52

    • Peer Reviewed
  • [Journal Article] Combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in colon cancer HT29 cells2008

    • Author(s)
      Yoshida T, Horinaka M, Takara M, Tsuchihashi M, Mukai N, Wakada M, Sakai T
    • Journal Title

      Environ Health Prev Med. 13

      Pages: 281-7

    • Peer Reviewed
  • [Journal Article] a sesquiterpene aminoquinone from a marine sponge, induces G1 arrest or apoptosis in different leukemia cells2008

    • Author(s)
      Kong D, Aoki S, Sowa Y, Sakai T, Kobayashi M. Smenospongine
    • Journal Title

      Mar Drugs 6

      Pages: 480-8

    • Peer Reviewed
  • [Journal Article] Anti-gout agent allopurinol exerts cytotoxicity to human hormone-refractory prostate cancer cells in combination with TRAIL2008

    • Author(s)
      Yasuda T, Yoshida T, Goda AE, Horinaka M, Yano K, Shiraishi T, Wakada M, Mizutani Y, Miki T, Sakai T
    • Journal Title

      Mol Cancer Res 6

      Pages: 1852-60

    • Peer Reviewed
  • [Journal Article] Baicalein overcomes TRAIL resistance via two different cell specific pathways in cancer cells but not in normal cells2008

    • Author(s)
      Taniguchi H, Yoshida T, Horinaka M, Yasuda T, Goda AE, Konishi M, Wakada M, Kataoka K, Yoshikawa T, Sakai T
    • Journal Title

      Cancer Res. 68

      Pages: 8918-27

    • Peer Reviewed
  • [Journal Article] Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis2008

    • Author(s)
      Yoshida T, Konishi M, Horinaka M, Yasuda T, Goda AE, Taniguchi H, Yano K, Wakada M, Sakai T
    • Journal Title

      Biochem Biophys Res Commun. 375

      Pages: 129-33

    • Peer Reviewed
  • [Journal Article] Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole2008

    • Author(s)
      Goda AE, Yoshida T, Horinaka M, Yasuda T, Shiraishi T, Wakada M, Sakai T
    • Journal Title

      Oncogene. 27

      Pages: 3455-45

    • Peer Reviewed
  • [Journal Article] a novel histone deacetylase inhibitor, exhibits antitumor activity with selective, sustained accumulation of acetylated histones in tumors in the WiDr xenograft model2008

    • Author(s)
      Shindoh N, Sowa Y(他13名), Sakai T(他13名)YM753
    • Journal Title

      Int J Oncol. 32

      Pages: 545-55

    • Peer Reviewed
  • [Journal Article] CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells2008

    • Author(s)
      Takagi K, Sowa Y, Cevik OM, Nakanishi R, Sakai T
    • Journal Title

      Int J Oncol. 32

      Pages: 1105-10

    • Peer Reviewed
  • [Journal Article] Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression2008

    • Author(s)
      Matsuzaki Y, Koyama M, Hitomi T, Yokota T, Kawanaka M, Nishikawa A, Germain D, Sakai T
    • Journal Title

      Oncol Rep. 19

      Pages: 721-7

    • Peer Reviewed
  • [Journal Article] Lipoxygenase inhibitors induce death receptor 5/TRAIL-R2 expression and sensitize malignant tumor cells to TRAIL-induced apoptosis2007

    • Author(s)
      Yoshida T, Shiraishi T, Horinaka M, Nakata S, Yasuda T, Goda AE, Wakada M, Mizutani Y, Miki T, Nishikawa A, Sakai T
    • Journal Title

      Cancer Sci 98

      Pages: 1417-23

    • Peer Reviewed
  • [Journal Article] Glycosylation modulates TRAIL-R1/death receptor 4 protein : different regulations of two pro-apoptotic receptors for TRAIL by tunicamycin2007

    • Author(s)
      Yoshida T, Shiraishi T, Horinaka M, Wakada M, Sakai T
    • Journal Title

      Oncol Rep. 18

      Pages: 1239-42

    • Peer Reviewed
  • [Journal Article] Identification of JTP-70902, a p15^<INK4b>-inductive compound, as a novel MEK1/2 inhibitor2007

    • Author(s)
      Yamaguchi T, Yoshida T, Kurachi R, Kakegawa J, Hori Y, Nanayama T, Hayakawa K, Abe H, Takagi K, Matsuzaki Y, Koyama M, Yogosawa S, Sowa Y, Yamori T, Tajima N, Sakai T
    • Journal Title

      Cancer Sci. 98

      Pages: 1809-16

    • Peer Reviewed
  • [Journal Article] The plant alkaloid cryptolepine induces p21^<WAF1/CIP1> and cell cycle arrest in a human osteosarcoma cell line2007

    • Author(s)
      Matsui TA, Sowa Y(他8名), Sakai T(他8名)
    • Journal Title

      Int J Oncol. 31

      Pages: 915-22

    • Peer Reviewed
  • [Journal Article] Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo2007

    • Author(s)
      Matsui TA, Murata H, Sakabe T, Sowa Y, Horie N, Nakanishi R, Sakai T, Kubo T
    • Journal Title

      Oncol Rep. 18

      Pages: 1263-8

    • Peer Reviewed
  • [Journal Article] a lignan of sesame, down-regulates cyclin D1 protein expression in human tumor cells2007

    • Author(s)
      Yokota T, Matsuzaki Y(他9名), Sakai T(他9名)Sesamin
    • Journal Title

      Cancer Sci. 98

      Pages: 1447-53

    • Peer Reviewed
  • [Journal Article] ZD1839 induces p15^<INK4b> and causes G1 arrest by inhibiting the MAPK/ERK pathway2007

    • Author(s)
      Koyama M, Matsuzaki Y, Yogosawa S, Hitomi T, Kawanaka M, Sakai T
    • Journal Title

      Mol Cancer Ther. 6

      Pages: 1579-87

    • Peer Reviewed
  • [Journal Article] Vitamin K2 inhibits the proliferation of HepG2 cells by up-regulating the transcription of p21 gene2007

    • Author(s)
      Liu W, Sakai T(他11名)
    • Journal Title

      Hepatol Res. 37

      Pages: 360-5

    • Peer Reviewed
  • [Journal Article] Halocynthiaxanthin and peridinin, two dietary carotenoids, sensitize colon cancer cell lines to the death ligand TRAIL2007

    • Author(s)
      Yoshida T, Maoka T, Das SK, Kanazawa K, Horinaka M, Wakada M, Satomi, Y, Nishino H, Sakai T
    • Journal Title

      Mol Cancer Res. 5

      Pages: 615-25

    • Peer Reviewed
  • [Journal Article] Prognostic significance of thymidylate synthase expression in patients with prostate cancer undergoing radical prostatectomy2007

    • Author(s)
      Li Y, Sakai T(他8名)
    • Journal Title

      Urology. 69

      Pages: 988-95

    • Peer Reviewed
  • [Journal Article] Chemotherapeutic drugs sensitize cancer cells to TRAIL-mediated apoptosis : up-regulation of DR5 and inhibition of Yin Yang 12007

    • Author(s)
      Baritaki S, Sakai T(他3名)
    • Journal Title

      Mol Cancer Ther. 6

      Pages: 1387-99

    • Peer Reviewed
  • [Journal Article] Fenretinide up-regulates DR5/TRAIL-R2 expression via the induction of the transcription factor CHOP and combined treatment with fenretinide and TRAIL induces synergistic apoptosis in colon cancer cell lines2007

    • Author(s)
      Kouhara J, Yoshida T, Nakata S, Horinaka M, Wakada M, Ueda Y, Yamagishi H, Sakai T
    • Journal Title

      Int J Oncol. 30

      Pages: 679-87

    • Peer Reviewed
  • [Journal Article] Oct-1 is involved in the transcriptional repression of the p15^<INK4b> gene2007

    • Author(s)
      Hitomi T, Matsuzaki Y, Yasuda S, Kawanaka M, Yogosawa S, Koyama M, Tantin D, Sakai T
    • Journal Title

      FEBS Lett. 581

      Pages: 1087-92

    • Peer Reviewed
  • [Journal Article] A novel synthetic drug, LB-18, closely related to lembehyne-A derived from a marine sponge, induces caspase-independent cell death to human neuroblastoma cells2006

    • Author(s)
      Izumi M, Yogosawa S, Aoki S, Watanabe H, Kamiyama J, Takahara Y, Sowa Y, Kobayashi M, Hosoi H, Sugimoto T, Sakai T
    • Journal Title

      Int J Oncol. 29

      Pages: 169-73

    • Peer Reviewed
  • [Journal Article] 15-Deoxy-Δ^<12, 14>-prostaglandin J_2 induces death receptor 5 expression through mRNA stabilization independently of PPARγ and potentiates TRAIL-induced apoptosis2006

    • Author(s)
      Nakata S, Yoshida T, Shiraishi T, Horinaka M, Kouhara J, Wakada M, Sakai T
    • Journal Title

      Mol Cancer Ther. 5

      Pages: 1827-35

    • Peer Reviewed
  • [Journal Article] The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand2006

    • Author(s)
      Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Sakai T
    • Journal Title

      Mol Cancer Ther. 5

      Pages: 945-51

    • Peer Reviewed
  • [Journal Article] Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells2006

    • Author(s)
      Matsui TA, Sowa Y, Yoshida T, Murata H, Horinaka M, Wakada M, Nakanishi R, Sakabe T, Kubo T, Sakai T
    • Journal Title

      Carcinogenesis. 27

      Pages: 1768-77

    • Peer Reviewed
  • [Journal Article] Lysocellin, a metabolite of the novel drug 'alopestatin', induces G1 arrest and prevents cytotoxicity induced by etoposide2006

    • Author(s)
      Takahara Y, Yogosawa S(他12名), Sakai T(他12名)
    • Journal Title

      Int J Oncol. 28

      Pages: 823-9

    • Peer Reviewed
  • [Journal Article] Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner2006

    • Author(s)
      Aoki S, Kong D, Suna H, Sowa Y, Sakai T, Setiawan A, Kobayashi M
    • Journal Title

      Biochem Biophys Res Commun. 342

      Pages: 101-6

    • Peer Reviewed
  • [Journal Article] Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells2006

    • Author(s)
      Hasegawa H, Yoshida T(他14名), Sakai T(他14名)
    • Journal Title

      Blood. 107

      Pages: 679-88

    • Peer Reviewed
  • [Journal Article] Galectin-1 interacts with the α5β1 fibronectin receptor to restrict carcinoma cell growth via induction of p21 and p272005

    • Author(s)
      Fischer C, Sakai T(他8名)
    • Journal Title

      J Biol Chem. 280

      Pages: 37266-77

    • Peer Reviewed
  • [Journal Article] Fucoxanthin induces cell cycle arrest at G_0/G_1 phase in human colon carcinoma cells through up-regulation of p21^<WAF1/Cip1>2005

    • Author(s)
      Das SK, Hashimoto T, Shimizu K, Yoshida T, Sakai T, Sowa Y, Komoto A, Kanazawa K
    • Journal Title

      Biochim Biophys Acta. 1726

      Pages: 328-35

    • Peer Reviewed
  • [Journal Article] Artepillin C in Brazilian propolis induces G_0/G_1 arrest via stimulation of Cip1/p21 expression in human colon cancer cells2005

    • Author(s)
      Shimizu K, Das SK, Hashimoto T, Sowa Y, Yoshida T, Sakai T, Matsuura Y, Kanazawa K
    • Journal Title

      Mol Carcinog. 44

      Pages: 293-9

    • Peer Reviewed
  • [Journal Article] Quercetin induces gadd45 expression through a p53-independent pathway2005

    • Author(s)
      Yoshida T, Maeda A, Horinaka M, Shiraishi T, Nakata S, Wakada M, Yogosawa S, Sakai T
    • Journal Title

      Oncol Rep. 14

      Pages: 1299-303

    • Peer Reviewed
  • [Journal Article] A new cancer diagnostic system based on a CDK profiling technology2005

    • Author(s)
      Ishihara H, Sowa Y(他16名), Sakai T(他16名)
    • Journal Title

      Biochem Biophys Acta. 1741

      Pages: 226-33

    • Peer Reviewed
  • [Journal Article] The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer HeLa cells2005

    • Author(s)
      Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Nakanishi R, Nishino H, Sakai T
    • Journal Title

      Biochem Biophys Res Commun 333

      Pages: 833-8

    • Peer Reviewed
  • [Journal Article] Luteolin induces apoptosis via death receptor 5 up-regulation in human malignant tumor cells2005

    • Author(s)
      Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Nakanishi R, Nishino H, Matsui H, Sakai T
    • Journal Title

      Oncogene. 24

      Pages: 7180-9

    • Peer Reviewed
  • [Journal Article] Tunicamycin enhances TRAIL-induced apoptosis in human prostate cancer cells2005

    • Author(s)
      Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T
    • Journal Title

      Cancer Res. 65

      Pages: 6364-70

    • Peer Reviewed
  • [Journal Article] 15-Deoxy-Δ^<12, 14>-prostaglandin J_2 activates the expression of p15^<INK4b> gene, a cyclin-dependent kinase inhibitor2005

    • Author(s)
      Matsuzaki Y, Koyama M, Hitomi T, Takaoka Y, Kawanaka M, Sakai T
    • Journal Title

      Int J Oncol. 27

      Pages: 497-503

    • Peer Reviewed
  • [Journal Article] Proteasome inhibitor MG132 induces death receptor 5 through CCAAT/enhancer-binding protein homologous protein2005

    • Author(s)
      Yoshida T, Shiraishi T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T
    • Journal Title

      Cancer Res. 65

      Pages: 5662-7

    • Peer Reviewed
  • [Journal Article] INK4 family-a promising target for'gene-regulating chemoprevention'and 'molecular-targeting prevention'of cancer-2005

    • Author(s)
      Matsuzaki Y, Sakai T
    • Journal Title

      Environ Health Prev Med 10

      Pages: 72-7

    • Peer Reviewed
  • [Journal Article] Inhibitory effects of cancer cell proliferation by novel histone deacetylase inhibitors involve p21/WAF1 induction and G2/M arrest2005

    • Author(s)
      Maeda T, Nagaoka Y, Kawai Y, Takagaki N, Yasuda C, Yogosawa S, Sowa Y, Sakai T, Uesato S
    • Journal Title

      Biol Pharm Bull. 28

      Pages: 849-53

    • Peer Reviewed
  • [Journal Article] Hes1 directly controls cell proliferation through the transcriptional repression of p27^<Kip1>2005

    • Author(s)
      Murata K, Sakai T(他6名)
    • Journal Title

      Mol Cell Biol. 25

      Pages: 4262-71

    • Peer Reviewed
  • [Journal Article] Differential response at the hGABP/E4TF1 site of retinoblastoma gene promoter in human testicular seminoma cells2005

    • Author(s)
      Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T, Sakai T
    • Journal Title

      Oncol Rep. 13

      Pages: 871-4

    • Peer Reviewed
  • [Journal Article] Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway2005

    • Author(s)
      Takagaki N, Sowa Y, Oki T, Nakanishi R, Yogosawa S, Sakai T
    • Journal Title

      Int J Oncol. 26

      Pages: 185-9

    • Peer Reviewed
  • [Presentation] インドール-3-カルビノールとゲニステイン併用による細胞死増強効果とそのメカニズム2009

    • Author(s)
      中村吉隆, 他
    • Organizer
      第79回日本衛生学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-03-30
  • [Presentation] ククルビタシンBによる活性酸素種を介した細胞周期停止及びアポトーシスの誘導2009

    • Author(s)
      安田周祐, 他
    • Organizer
      第79回日本衛生学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-03-30
  • [Presentation] イソリキリチゲニンはヒト大腸癌細胞に対してTRAIL誘導性アポトーシスを増強する2009

    • Author(s)
      堀中真野, 他
    • Organizer
      第79回日本衛生学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-03-30
  • [Presentation] 発癌分子を標的とした合理的癌予防法の基礎的研究2008

    • Author(s)
      酒井敏行
    • Organizer
      第78回日本衛生学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2008-03-30
  • [Presentation] baicaleinはDR5発現を上昇させ癌細胞特異的にTRAIL誘導性アポトーシスを増強する2008

    • Author(s)
      谷口浩也, 他
    • Organizer
      第78回日本衛生学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2008-03-30
  • [Presentation] ホルモン非依存性前立腺癌に対するアロプリノールのtumor necrosis factor-related apoptosis-inducing ligand(TRAIL)を介したアポトーシスの増強2008

    • Author(s)
      安田考志, 他
    • Organizer
      第78回日本衛生学会総会
    • Place of Presentation
      熊本
    • Year and Date
      2008-03-30
  • [Presentation] 15-Deoxy-Δ^<12, 14>-PGJ_2はDR5のmRNAを安定化させて誘導し、TRAILによる腫瘍細胞へのアポトーシスを増強する2007

    • Author(s)
      若田未来, 他
    • Organizer
      第77回日本衛生学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-28
  • [Presentation] カロテノイドhalocynthiaxanthinは抗腫瘍性リガンドTRAILによる大腸癌細胞へのアポトーシスを増強する2007

    • Author(s)
      吉田達士, 他
    • Organizer
      第77回日本衛生学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-28
  • [Presentation] アピゲニンはDR5遺伝子の発現を誘導し、TRAIL誘導性アポトーシスを増強する2007

    • Author(s)
      堀中真野, 他
    • Organizer
      第77回日本衛生学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-28
  • [Presentation] 癌の「分子標的併用予防法」の開発-ルテオリンによるDR5遺伝子の発現誘導とTRAIL誘導性アポトーシスの増強-2006

    • Author(s)
      堀中真野, 他
    • Organizer
      第76回日本衛生学会総会
    • Place of Presentation
      山口
    • Year and Date
      2006-03-26
  • [Presentation] 癌の「分子標的併用予防法」の開発-FenretinideによるDR5遺伝子の発現誘導とTRAIL誘導性アポトーシスの増強-2006

    • Author(s)
      甲原純二, 他
    • Organizer
      第76回日本衛生学会総会
    • Place of Presentation
      山口
    • Year and Date
      2006-03-26
  • [Presentation] S状結腸粘膜mRNA発現量測定による大腸癌高危険度指標の開発2006

    • Author(s)
      石川秀樹, 他
    • Organizer
      第76回日本衛生学会総会
    • Place of Presentation
      山口
    • Year and Date
      2006-03-26
  • [Presentation] アルクチインによるサイクリンD1発現抑制2006

    • Author(s)
      松崎洋一郎, 他
    • Organizer
      第76回日本衛生学会総会
    • Place of Presentation
      山口
    • Year and Date
      2006-03-26
  • [Presentation] カイメン由来物質がヒト神経芽腫細胞株に細胞死を誘導する2006

    • Author(s)
      和泉守篤, 他
    • Organizer
      第76回日本衛生学会総会
    • Place of Presentation
      山口
    • Year and Date
      2006-03-26
  • [Book] アンチエイジング・ヘルスフード2008

    • Author(s)
      曽和義広
    • Total Pages
      7
    • Publisher
      サイエンスフォーラム
  • [Remarks]

    • URL

      http://www.f.kpu-m.ac.jp/k/pubmed/

URL: 

Published: 2010-06-10   Modified: 2016-04-21  

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