Reviews, Commentaries, etc. - Arai, Midori

リグナン骨格を有する神経幹細胞分化促進剤の創成研究

三瓶 真菜, 荒井 緑, 菅波 晃子, 田村 裕, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  138年会 ( 2 ) 115 - 115 2018.03

ISSN  0918-9823

Amonum villosum等からのTRAIL耐性克服作用を持つ天然物の探索

石川龍翔, PRAPAIRAT Seephonkai, PRAPAIRAT Seephonkai, 荒井緑, SAMIR K. Sadhu, FIROJ Ahmed, 小谷野喬, THAWORN Kowithayakorn, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am273S 2018

放線菌Nocardia属からの新規二次代謝産物の探索

小林菜摘, 原康雅, 荒井緑, 五ノ井透, 矢口貴志, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am256S 2018

放線菌二次代謝産物からのBMI1プロモーター阻害剤の探索

横山夕将, 荒井緑, 石橋正己

日本薬学会年会要旨集(CD-ROM) 138th   ROMBUNNO.27PA‐am255S 2018

Beaumontia murtoniiなどからのBMI1プロモーター阻害剤の探索及び活性評価

金田結, 石川直樹, 荒井緑, 當銘一文, 小谷野喬, KOWITHAYAKORN Thaworn, 千葉哲博, 岩間厚志, 石橋正己

天然薬物の開発と応用シンポジウム講演要旨集 21st   105‐107 2016.10

ISSN  0919-2085

Polyalthia cerasoidesからのWntシグナル阻害する新規アルカロイド

庄野 巧, 石川 直樹, 當銘 一文, 荒井 緑, 枡 飛雄真, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本生薬学会年会講演要旨集 ((一社)日本生薬学会)  63回   179 - 179 2016.08

ISSN  0919-1992

Polyalthia cerasoidesからのWntシグナルを阻害する天然物の探索

庄野 巧, 石川 直樹, 當銘 一文, 荒井 緑, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 124 - 124 2016.03

ISSN  0918-9823

TRAIL耐性克服作用を有するFuligocandin Bの標的タンパク質同定と作用機序解析に向けた研究

荒井 緑, 田口 翔大, 佐藤 守, 荷堂 清香, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 117 - 117 2016.03

ISSN  0918-9823

ヒストン修飾に関わるポリコーム構成分子BMI1を標的とした天然物の探索

金田 結, 石川 直樹, 當銘 一文, 荒井 緑, 小谷野 喬, Kowithayakorn Thaworn, 石橋 正己

日本薬学会年会要旨集 ((公社)日本薬学会)  136年会 ( 2 ) 59 - 59 2016.03

ISSN  0918-9823

Target Identification and Mode of Action of 5'-I Fuligocandin B with TRAIL-resistance Overcoming Activity

Arai Midori A., Taguchi Shota, Komatsuzaki Kazuhiro, Uchiyama Kento, Masuda Ayaka, Satoh Mamoru, Kado Sayaka, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  58 ( 0 ) Oral15 2016

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<p> Fuligocandin A (1) and B (2) are novel natural cycloanthranilylproline derivatives isolated from Fuligo candida. We found the ability of 2 to overcome TRAIL-resistance of cancer cells. Enatiometically pure Fuligocandin B (2) and its derivative 5'-I Fuligocandin B (9) were synthesized, and the latter had an improved TRAIL-resistance overcoming activity against AGS cells. A biotin probe of 9 that had a photo-activatable aryl diazirine group was synthesized, and a pull-down assay revealed that Valosin-containing protein (VCP/p97), an AAA+ ATPase, was a target protein of 9. Knock-down of VCP by siRNA enhanced sensitivity to TRAIL in AGS cells. In addition, 9 enhanced ubiqutination of proteins and CHOP expression, which was a regulator of DR5. These data suggest that ER stress caused by VCP inhibition by 9 increases CHOP-mediated DR5 up regulation, which enhances TRAIL induced cell death. To the best of our knowledge, this is the first experimental data linking VCP and TRAIL-resistance overcoming activity in cancer cells. </p>

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Hibiscus ficulneusからのWntシグナル阻害作用をもつ天然物の探索

SHONO TAKUMI, ISHIKAWA NAOKI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR KUMAR, AHMED FIROJ, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 135th   ROMBUNNO.27PB-PM168 2015

Search for activator of neural stem cells differentiation based on inhibition of Notch-Hes signaling pathway

Arai Midori.A, Akamine Ryuta, Yoneyama Tatsuro, Okamoto Ryuichi, Koyano Takashi, Kowithayakorn Thaworn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  57 ( 0 ) PosterP1 2015

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<p> Basic helix-loop-helix (bHLH) repressor- and activator-type transcription factors play essential roles in proliferation and differentiation of neural stem cells (NSCs). Hes1 and Hes5, bHLH repressor-type factors, lead NSCs to remaining undifferentiation. The transcription of Hes1 and Hes5 are regulated by Notch signaling pathway. Therefore, inhibition of Notch signaling pathway would accelerate NSCs differentiation into neurons and glial cells. To find inhibitors of Notch signaling pathway from natural resources, we constructed a cell-based reporter assay of NICD-mediated transcription.</p><p>By using this assay system, we isolated twelve xanthones (1-12) including a new compound (12) from Garcinia speciosa (bark). Structure of 12was elucidated by spectroscopic data analyses. Among the isolated compounds, 2strongly inhibited the transcriptional activity of NICD. Western blot analysis of 2showed decrease in Hes1 and Hes5 protein expression. NICD was also decreased, but NotchDE was increased. These results suggested that 2inhibits Notch signaling pathway by the inhibition of g-secretase.</p><p> Five cardenolide glycosides (13-17) were isolated from Nerium indicum (leaves). 13inhibited the transcriptional activity of NICD with IC₅₀ values of 0.12 mM. Western blot analysis of 13showed decrease in Hes1 and Hes5 protein expression. Uscharin (18) and calotropin (19) were also found as Notch signaling inhibitors. Next, we examined the effect of 13, 18 and 19on NSCs differentiation. These compounds accelerated differentiation of mouse NSCs (MEB5) into neurons and glial cells.</p>

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Search for activator of neural stem cells differentiation based on inhibition of Notch-Hes signaling pathway

Arai Midori.A, Akamine Ryuta, Yoneyama Tatsuro, Okamoto Ryuichi, Koyano Takashi, Kowithayakorn Thaworn, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  57 ( 0 )  2015

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&lt;p&gt; Basic helix-loop-helix (bHLH) repressor- and activator-type transcription factors play essential roles in proliferation and differentiation of neural stem cells (NSCs). Hes1 and Hes5, bHLH repressor-type factors, lead NSCs to remaining undifferentiation. The transcription of Hes1 and Hes5 are regulated by Notch signaling pathway. Therefore, inhibition of Notch signaling pathway would accelerate NSCs differentiation into neurons and glial cells. To find inhibitors of Notch signaling pathway from natural resources, we constructed a cell-based reporter assay of NICD-mediated transcription.&lt;/p&gt;&lt;p&gt;By using this assay system, we isolated twelve xanthones (1-12) including a new compound (12) from Garcinia speciosa (bark). Structure of 12was elucidated by spectroscopic data analyses. Among the isolated compounds, 2strongly inhibited the transcriptional activity of NICD. Western blot analysis of 2showed decrease in Hes1 and Hes5 protein expression. NICD was also decreased, but NotchDE was increased. These results suggested that 2inhibits Notch signaling pathway by the inhibition of g-secretase.&lt;/p&gt;&lt;p&gt; Five cardenolide glycosides (13-17) were isolated from Nerium indicum (leaves). 13inhibited the transcriptional activity of NICD with IC&lt;sub&gt;50&lt;/sub&gt; values of 0.12 mM. Western blot analysis of 13showed decrease in Hes1 and Hes5 protein expression. Uscharin (18) and calotropin (19) were also found as Notch signaling inhibitors. Next, we examined the effect of 13, 18 and 19on NSCs differentiation. These compounds accelerated differentiation of mouse NSCs (MEB5) into neurons and glial cells.&lt;/p&gt;

Tabernaemontana divaricataからのWntシグナルを阻害する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, SAMIR K SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 135th   ROMBUNNO.27PB-PM210S 2015

Eurycoma longifolia等からのWntシグナルを阻害する天然物の探索

OISHI KENSUKE, TOUME KAZUFUMI, ARAI MIDORI, MIZOGUCHI TAKAMASA, ITO MOTOYUKI, SADHU SAMIR K, AHMED FIROJ, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

天然薬物の開発と応用シンポジウム講演要旨集 20th   69 - 71 2014.11

ISSN  0919-2085

Artocarpus communis由来のTRAIL耐性克服作用をもつプレニルフラボン成分

HABU TADASHI, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, KOWITHAYAKORN, THAWORN, ISHIBASHI MASAMI

香料・テルペンおよび精油化学に関する討論会講演要旨集 58th   307 - 309 2014.09

Hibiscus ficulneusからのWntシグナル阻害作用を持つ天然物の探索

SHONO TAKUMI, TOUME KAZUFUMI, ARAI MIDORI, SADHU SAMIR K, AHMED FIROJ, ISHIBASHI MASAMI

日本生薬学会年会講演要旨集 61st   181 2014.08

ISSN  0919-1992

Search for bioactive natural products that inhibit Wnt signaling pathway from Calotropis giantea and Xylocarpus granatum

Toume Kazufumi, Park Hyun Young, Kamiya Kentaro, Arai Midori, Samir K. Sadhu, Firoj Ahmed, Ishibashi Masami

Symposium on the Chemistry of Natural Products, symposium papers (Symposium on the Chemistry of Natural Products Steering Committee)  56 ( 0 )  2014

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&lt;p&gt;Wnt signaling pathway has a key roles in various cellular process such as cell proliferation and tissue maintenance. Aberrant activation of Wnt signal can initiate the development of several diseases including cancer, Alzheimer&#039;s disease, and diabetes. Using cell-based luciferase screening assay system for a Wnt signaling pathway (TCF/β-catenin transcription), activity-guided exploration of our natural resources extracts library were conducted. Detailed investigation on mode of action of isolated compounds were also carried out.&lt;/p&gt;&lt;p&gt;Six cardenolides (1-6) were isolated from the methanol extract of Calotropis gigantea (Asclepiadaceae) exudate, and compounds 1, 3, 5, and 6 strongly inhibited TCF/β-catenin transcription activity (IC&lt;sub&gt;50&lt;/sub&gt;0.7-3.8 nM). Compounds 1, and 3-6showed potent cytotoxicity (IC&lt;sub&gt;50&lt;/sub&gt; 1.8-7.0 nM) against Wnt dependent colon cancer cell (SW480, DLD1, HCT116), without cytotoxicity against RKO (Wnt independent colon cancer) cells. Calotropin (1) inhibited Wnt signaling by reducing both nuclear and cytosolic β-catenin levels in SW480 cells. Further investigation using inhibitors revealed that 1 potentiate the degradation of β-catenin by increasing the phosphorylation of β-catenin at Ser45 mediated by casein kinase 1α (CK1α). Moreover, 1 significantly enhanced CK1α protein and mRNA levels.&lt;/p&gt;&lt;p&gt;Three limonoides (7-9) were isolated from methanol extract of Xylocarpus granatum (Meliaceae) leaves, including two new limonoids, named as xylogranin A (7) and B (8). Compounds 7 and 8 inhibited TCF/β-catenin transcription activity. Treatment of SW480 cells with 8 led to a significant decrease of β-catenin in nuclei but not in the cytosol, and c-myc and PPARδ, target proteins of Wnt signaling pathway. These results indicated that a decrease of β-catenin in nuclei by 8contributed the Wnt inhibition of 8.&lt;/p&gt;

Calotropis gigantea由来カルデノリドCalotropinのウィントシグナル阻害作用

BOKU KEN'EI, TOUME KAZUFUMI, ARAI MIDORI, SAMIR K. SADHU, FIROJ AHMED, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 134th   ROMBUNNO.29AMM-126 2014

Artocarpus communis由来プレニルフラボノイドのTRAIL耐性克服作用

HABU OSAMU, TOUME KAZUFUMI, ARAI MIDORI, KOYANO TAKASHI, THAWORN KOWITHAYAKORN, ISHIBASHI MASAMI

日本薬学会年会要旨集(CD-ROM) 134th   ROMBUNNO.28M-AM05S 2014