Sugimoto, Yoshikazu

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 化学療法学講座 （Shiba-Kyoritsu）

Position

Professor

Related Websites

External Links
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Academic Background 【 Display / hide 】

  • 1980.03

    The University of Tokyo, Faculty of Pharmaceutical Science, 薬学科

    Japan, University, Graduated

  • 1985.03

    The University of Tokyo, Graduate School of Pharmaceutical Sciences, 生命薬学専攻

    Japan, Graduate School, Completed, Doctoral course

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Research Areas 【 Display / hide 】

  • Medical pharmacy (Clinical Pharmaceutical Science)

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Research Keywords 【 Display / hide 】

  • ABC transporter

  • molecular targer therapy

  • anticancer drug resistance

  • gene therapy

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Books 【 Display / hide 】

  • がん化学療法・分子標的治療update.

    杉本芳一., 中外医学社, 東京, 2009.10

    Scope: 59-63

  • がん薬物療法学.

    杉本芳一., 大阪/日本臨床社, 2009.01

    Scope: 349-355

  • がんの分子標的治療.

    '野口耕司, 杉本芳一.', 東京/南山堂, 2008.09

    Scope: 278-290

  • 薬剤師生涯研修ガイド.

    杉本芳一., 東京/学校法人医学アカデミー出版部, 2008.05

    Scope: 223-224

  • 薬学の未来を拓く.

    杉本芳一., 東京/慶應義塾, 2008.04

    Scope: 72-81

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Papers 【 Display / hide 】

  • Cytotoxicity of cucurbitacin E from Citrullus colocynthis against multidrug-resistant cancer cells

    Saeed M., Boulos J., Elhaboub G., Rigano D., Saab A., Loizzo M., Hassan L., Sugimoto Y., Piacente S., Tundis R., Yagi S., Khalid H., Efferth T.

    Phytomedicine （Phytomedicine)  62 2019.09

    ISSN  09447113

    　View Summary

    © 2019 Elsevier GmbH Background: Cucurbitacin E (CuE) is an oxygenated tetracyclic triterpenoid isolated from the fruits of Citrullus colocynthis (L.) Schrad. Purpose: This study outlines CuE's cytotoxic activity against drug-resistant tumor cell lines. Three members of ABC transporters superfamily, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and ABCB5 were investigated, whose overexpression in tumors is tightly linked to multidrug resistance. Further factors of drug resistance studied were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Methods: Cytotoxicity assays (resazurin assays) were used to investigate the activity of Citrullus colocynthis and CuE towards multidrug resistant cancer cells. Molecular docking (In silico) has been carried out to explore the CuE's mode of binding to ABC transporters (P-gp, BCRP and ABCB5). The visualization of doxorubicin uptake was done by a Spinning Disc Confocal Microscope. The assessment of proteins expression was done by western blotting analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to cucurbitacins (CuA, CuB, CuE, CuD, CuI, and CuK). Results: Multidrug-resistant cells overexpressing P-gp or BCRP were cross-resistant to CuE. By contrast, TP53 knock-out cells were sensitive to CuE. Remarkably, resistant cells transfected with oncogenic ΔEGFR or ABCB5 were hypersensitive (collateral sensitive) to CuE. In silico analyses demonstrated that CuE is a substrate for P-gp and BCRP. Immunoblot analyses highlighted that CuE targeted EGFR and silenced its downstream signaling cascades. The most striking result that emerged from the doxorubicin uptake by ABCB5 overexpressing cells is that CuE is an effective inhibitor for ABCB5 transporter when compared with verapamil. The COMPARE analyses of transcriptome-wide expression profiles of tumor cell lines of the NCI identified common genes involved in cell cycle regulation, cellular adhesion and intracellular communication for different cucurbitacins. Conclusion: CuE represents a potential therapeutic candidate for the treatment of certain types of refractory tumors. To best of our knowledge, this is the first time to identify CuE and verapamil as inhibitors for ABCB5 transporter.

  • Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells

    Hegazy M., Abdelfatah S., Hamed A., Mohamed T., Elshamy A., Saleh I., Reda E., Abdel-Azim N., Shams K., Sakr M., Sugimoto Y., Paré P., Efferth T.

    Phytomedicine （Phytomedicine)  59 2019.06

    ISSN  09447113

    　View Summary

    © 2018 Background: The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells. Purpose: We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines. Material and methods/study design: Methylene chloride: methanol (1:1) and methanol: H 2 O (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically. Results: Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC 50 values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts. Conclusion: The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.

  • Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression

    Saeed M., Rahama M., Kuete V., Dawood M., Elbadawi M., Sugimoto Y., Efferth T.

    Phytomedicine （Phytomedicine)  59 2019.06

    ISSN  09447113

    　View Summary

    © 2019 Background: In the drug discovery field, natural products deemed a precious source of novel lead compounds. They have the ability to bypass or overcome multidrug resistance (MDR) in cancer cells. Purpose: In this study, the natural polyphenolic stilbene resveratrol (RES) has been studied for its cytotoxic activity toward MDR cancer cells. Methods: Resazurin assay was used to investigate the cytotoxicity of RES not only against a panel of drug-resistant cancer cells overexpressing P-glycoprotein/ABCB1, BCRP/ABCG2, ABCB5 (ATP-binding cassette transporters), but also mutation-activated EGFR. The assessment of proteins expression was done by Western blot analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to RES. The NF-κB activation was evaluated using NF-kB reporter cells assay. Results: Interestingly, MDR cells overexpressing ABCB5 and mutation-activated EGFR were collateral sensitive (CS) to RES. Our immunoblotting analysis highlighted that CS may be attributed to RES-induced sirtuin 1 (SIRT1) overexpression. Indeed, the SIRT1 inhibitor, sirtinol completely abolished CS to RES, indicating a causative role of SIRT1 for CS to RES. In addition, COMPARE and hierarchical cluster analyses of transcriptomic data indicated genes associated with diverse cellular mechanisms ranging from the immune response, inflammation signaling, and microtubule formation to cell migration. Searching for transcription factor binding motifs in the promoters of these genes pointed to NF-κB as one of the master regulators related to RES activity. Conclusion: The findings demonstrate that RES alone or in combination with established chemotherapeutic agents might overcome the refractory tumors. This information may be immensely useful for the development of personalized treatment.

  • Novel pharmacological effects of poly (ADP-ribose) polymerase inhibitor rucaparib on the lactate dehydrogenase pathway

    Nonomiya Y., Noguchi K., Katayama K., Sugimoto Y.

    Biochemical and Biophysical Research Communications （Biochemical and Biophysical Research Communications)  510 （ 4 ） 501 - 507 2019.03

    ISSN  0006291X

    　View Summary

    © 2019 Elsevier Inc. Poly (ADP-ribose) polymerases (PARPs) are involved in various cellular events, including DNA repair. PARP inhibitors including olaparib and rucaparib, have been specially developed against breast and ovarian cancers deficient in DNA repair systems. In this study, we found that PARP1-defective olaparib-resistant A2780 cells (ola-R cells) cells were still sensitive to two PARP inhibitors, rucaparib and veliparib. Metabolomic analysis revealed that rucaparib suppressed the lactate dehydrogenase (LDH)-mediated conversion of pyruvic acid to lactic acid in A2780 cells, although olaparib did not. The inhibition of LDH by siRNA-mediated knockdown or by LDH inhibitors suppressed the growth of ovarian cancer cells. Our results suggested that the suppression of the LDH-associated pathway contributed to the pharmacological effects of rucaparib.

  • Synthesis of 5-hydroxy-3’,4’,7-trimethoxyflavone (HTMF) and related compounds and elucidation of their reversal effects on BCRP/ABCG2-mediated anticancer drug resistance.

    Tsunekawa R, KatayamaK, Hanaya K, Higashibayashi S, Sugimoto Y, Sugai T.

    CalBioChem 20 （ 2 ） 210 - 220 2019.01

    Research paper (scientific journal), Joint Work, Accepted

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics.

    Noguchi K, Katayama K, Sugimoto Y*.

    Pharmacogenomics and Personalized Medicine (Dove medical Press)  7   53-64 2014.02

    Introduction and explanation (scientific journal), Joint Work

  • トランスポーターの遺伝子多型.

    杉本芳一.

    がん分子標的治療 (メディカルレビュー社)  9(3)   29-35 2011.07

    Introduction and explanation (scientific journal), Single Work

  • 分子標的薬.

    杉本芳一.

    薬局 (南山堂)  61(2)   11 2010.02

    Introduction and explanation (scientific journal), Single Work

  • 抗悪性腫瘍薬の薬理学・薬力学・薬理遺伝学ー薬物相互作用.

    杉本芳一.

    日本臨床 (日本臨床社)  67, Suppl 1   349-355 2009.01

    Introduction and explanation (scientific journal), Single Work

  • 抗癌剤開発における民族差について.

    杉本芳一.

    臨床評価 (/臨床評価刊行会)  33(2)   393-398 2006.04

    Introduction and explanation (scientific journal), Single Work

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Presentations 【 Display / hide 】

  • High and low affinity kinetics of OATP2B1 - Inhibitory potency and pH-dependency of inhibitors -.

    Sato R, Akiyoshi T, Imaoka A, Katayama K, Sugimoto Y, Ohtani H.

    日本薬物動態学会第34回年会, 2019.12, Poster (general)

  • CAGE transcriptome analysis reveals BCL2A1 upregulation in FLT3-ITD/D835 dual mutated AML cells harboring complex co-mutations.

    Yamatani K, Ai T, Saitoh K, Yang H, Suzuki K, Hori A, Murakami-Tonami, Y, Zhang W, Carter B, Kinjo S, Ikeo K, Katayama K, Sugimoto Y, Harada H, Miida T, Shah NP, Konopleva M, Hayashizaki Y, Andreeff M, Yoko Y.

    61st ASH Annual Meeting (Orland, FL, USA) , 2019.12, Poster (general)

  • Transactivation of CD274/PD-L1 Gene Promoter by KSHV RTA/ORF50 and Cellular SP1 Proteins.

    Noguchi K, Miyazawa M, Katayama K, Sugimoto Y.

    第67回日本ウイルス学会 (東京都) , 2019.10, Poster (general)

  • かんきつ果汁中の新規 OATP2B1 阻害成分の探索とその阻害活性の定量的評価.

    森田時生, 秋好健志, 矢島広大, 今岡鮎子, 植草義徳, 木内文之, 片山和浩, 杉本芳一, 大谷壽一.

    第13回次世代を担う若手医療薬科学シンポジウム (岐阜市) , 2019.10, Poster (general)

  • 上皮間葉転換に伴って誘導されるside population細胞の制御.

    加藤優, 近藤慎吾, 杉本芳一.

    第78回日本癌学会学術総会 (京都市) , 2019.09, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Analysis of the resistance mechanisms to molecular-targeting anticancer agents

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉本　芳一, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Identification of factors regulating the capacity for both self-renewal and pluripotent differentiation of cancer stem cells and application to cancer treatment.

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 杉本　芳一, Grant-in-Aid for Challenging Exploratory Research, Principal Investigator

    　View Summary

    SP(+) cells have a property of Hoechst 33342 exclusion and are considered as stem-like cells. SP(+) cells isolated from human colorectal cancer 116/slug-25 cells showed higher expression of drug efflux transporter ABCG2 and histone acetyl transferase HAT1, and lower expression of histone methyltransferase EZH2 than SP(-) cells. Treatment of 116/slug-25 cells with inhibitors of histone acetyltransferases and methyltransferases diminished SP(+) cells. Genes regulating this SP(+) phenotype have been identified from a screening with shRNA library.

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD: (CHEMOTHERAPY)

    2020

  • SEMINAR: (CHEMOTHERAPY)

    2020

  • RESEARCH FOR BACHELOR'S THESIS 1

    2020

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2020

  • PHARMACEUTICAL SCIENCES OF DISEASES

    2020

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