Faculty Profiles - KUMAZOE MOTOFUMI

Information

写真a

KUMAZOE MOTOFUMI

Organization

Faculty of Agriculture Department of Bioscience and Biotechnology Assistant Professor

Contact information

Tel

0928024747

Profile

Most of my research focuses on the role of cGMP in the beneficial effects of phytochemicals. Our group also identified several molecules including Tollip and demonstrated that those signaling pathway-induced by cGMP play crucial role in the resilience of the human body.

Homepage

http://www.agr.kyushu-u.ac.jp/lab/syokuryo/
食糧化学研究室 HP
https://www.researchgate.net/profile/Motofumi-Kumazoe
Researchgate

External link

Research Interests・Research Keywords

Research theme： cGMP

Keyword： cGMP

Research period： 2024
Research theme： My research focuses on the role of cGMP in the physiological effects of phytochemicals. Our group previously identified several molecules including Tollip and demonstrated that those signaling pathways-induced by cGMP play crucial role in the resilience of the human body. To understand the physiological role of the cGMP in the beneficial effect of several compounds including phytochemicals, we use several disease mouse models including orthotopic tumor implantation model (Osteosarcoma, MPM, Pancreatic cancer, Lung cancer, breast cancer, etc) and other disease models (Obesity, SLE, IBD, ARDS, IgAN, NASH, PAH, Parkinson’s disease, Rheumatoid arthritis). Based on our findings, our recent clinical study found that GT-gH (our proposed polyphenols combination based by cGMP induction) suppressed weight gain and BMI increase in human subjects (UMIN000040109 Placebo-controlled, randomized, double-blind). My goal is to establish the novel strategy to prevent and treat the difficult diseases.

Keyword： cGMP, Phytochemicals, Chemical biology, Immunology, Oncology

Research period： 2021.12 - 2022.6

Awards

令和3年度日本農芸化学会西日本支部奨励賞

2022.1 日本農芸化学会西日本支部緑茶カテキンEGCGのcGMPを介した生体調節作用
令和3年度日本農芸化学会西日本支部奨励賞 (一般)

2022.1 日本農芸化学会西日本支部緑茶カテキンEGCGのcGMPを介した生体調節作用

熊添基文

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日本農芸化学会トピックス賞

2021.3 日本農芸化学会植物マイクロRNAの肺線維化抑制作用
がん研究助成奨励金

2018.3 日本対がん協会 cGMPによる癌幹細胞抑制機構の解明
日本農芸化学会トピックス賞

2017.3 日本農芸化学会新規膵臓がん幹細胞制御分子の同定
ネスレ栄養科学学会（NNCJ）2014 年度論文賞

2014.11 Nestlé Nutrition Council Japan 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis
平成25年度生物資源環境科学府賞

2014.3 九州大学大学院生物資源環境科学府緑茶ポリフェノールEpigallocatechin-3-ο-gallateによるがん細胞特異的な細胞致死誘導機構に関する研究
育志賞

2014.2 日本学術振興会緑茶ポリフェノールEpigallocatechin-gallateによるがん細胞特異的な細胞致死誘導機構の解明
平成25年度日本農芸化学会西日本支部奨励賞 (学生)

2014.1 日本農芸化学会西日本支部緑茶カテキンレセプター67-kDa Laminin Receptorが引き起こす癌細胞致死経路の発見とその増強
日本農芸化学会トピックス賞

2013.3 日本農芸化学会蛍光プローブ化緑茶カテキン EGCG を用いたがん細胞の特異的可視化
平成24年度日本栄養・食糧学会　九州・沖縄支部　優秀発表者賞

2012.9 日本栄養・食糧学会　九州・沖縄支部大会 Epigallocatechin-3-O-gallate(EGCG)によって活性化されるアポトーシス誘導経路の発見
9. The 4th International Conference on O-CHA (Tea) Culture and Science Symposium Poster Award.

2010.10 ICOS Phosphodiesterase V selective inhibitor enhances pro-apoptotic effect of EGCG by enforcing EGCG signaling pathway through the 67 LR.

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Papers

Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies. Reviewed International journal

Zhen Lu, Ioannis Verginadis, Motofumi Kumazoe, Gerardo M Castillo, Yao Yao, Rebecca E Guerra, Sandra Bicher, Menghao You, George McClung, Rong Qiu, Zebin Xiao, Zhen Miao, Subin S George, Daniel P Beiting, Takashi Nojiri, Yasutake Tanaka, Yoshinori Fujimura, Hiroaki Onda, Yui Hatakeyama, Akiko Nishimoto-Ashfield, Katrina Bykova, Wei Guo, Yi Fan, Nikolay M Buynov, J Alan Diehl, Ben Z Stanger, Hirofumi Tachibana, Terence P Gade, Ellen Puré, Constantinos Koumenis, Elijah M Bolotin, Serge Y Fuchs

Science translational medicine 16 ( 761 ) eadn0904 2024.8 （ ISSN:1946-6234 eISSN:1946-6242 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Science Translational Medicine

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.

DOI： 10.1126/scitranslmed.adn0904

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Fustin suppressed melanoma cell growth via cAMP/PKA-dependent mechanism. Reviewed International journal

Motofumi Kumazoe, Yoshinori Fujimura, Yu Shimada, Hiroaki Onda, Yui Hatakeyama, Hirofumi Tachibana

Bioscience, biotechnology, and biochemistry 88 ( 8 ) 900 - 907 2024.6 （ ISSN:0916-8451 eISSN:1347-6947 ）

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Bioscience, Biotechnology and Biochemistry

Melanoma, a cancer arising from melanocytes, requires a novel treatment strategy because of the ineffectiveness of conventional therapies in certain patients. Fustin is a flavanonol found in young fustic (Cotinus coggygria). However, little is known about its antimelanoma effects. Our study demonstrates that fustin suppresses the growth of B16 melanoma cells. Phalloidin staining of cytoskeletal actin revealed that fustin induced a conformational change in the actin structure of melanoma cells, accompanied by suppressed phosphorylation of myosin regulatory light chain 2 (MLC2), a regulator of actin structure. Furthermore, the protein kinase A (cAMP-dependent protein kinase) inhibitor H89 completely attenuated fustin-induced downregulation of phosphorylated myosin phosphatase targeting subunit 1, which is involved in dephosphorylation of MLC2. In a mouse model, administration of fustin suppressed tumor growth in B16 melanoma cells without adverse effects. In conclusion, our findings suggest that fustin effectively suppresses melanoma cell growth both in vitro and in vivo.

DOI： 10.1093/bbb/zbae072

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miR-12135 ameliorates liver fibrosis accompanied with downregulation of ITGA11. Reviewed International journal

Kumazoe Motofumi, Miyamoto Emi, Oka Chihiro, Kondo Miyuki, Yoshitomi Ren, Onda Hiroaki, Shimada Yu, Fujimura Yoshinori, Tachibana Hirofumi.

iScience 108730 ( 1 ) 108730 - 108730 2023.12 （ ISSN:2589-0042 eISSN:2589-0042 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

Cirrhosis is becoming one of the most common diseases worldwide. Abnormal upregulation of transforming growth factor β (TGF-β) signaling plays a pivotal role in the excess activation of hepatic stellate cells. However, an efficient countermeasure against abnormal hepatic stellate cell activation is yet to be established because TGF-β signaling is involved in several biological processes. Herein, we demonstrated the antifibrotic effect of miR-12135, a microRNA with unknown function upregulated by isoflavone. Comprehensive transcriptome assay demonstrated that miR-12135 suppressed Integrin Subunit Alpha 11 (ITGA11) and that ITGA11 expression is correlated with alpha smooth muscle actin expression in patients with cirrhosis. miR-12135 suppressed the expression level of ITGA11 and liver fibrosis. Importantly, ITGA11 is overexpressed in activated hepatic stellate cells, whereas ITGA11 knockout mice are viable and fertile. In conclusions, the miR-12135/ITGA11 axis can be an ideal therapeutic target to suppress fibrosis by precisely targeting abnormally upregulated TGF-β signaling in hepatic stellate cells.

DOI： 10.1016/j.isci.2023.108730

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Other Link： https://www.sciencedirect.com/science/article/pii/S2589004223028079
PPAR/PDK4 pathway is involved in the anticancer effects of cGMP in pancreatic cancer. Reviewed International journal

Mai Yamashita, Motofumi Kumazoe, Hiroaki Onda, Shun Hiroi, Yu Shimada, Yoshinori Fujimura, Hirofumi Tachibana

Biochemical and biophysical research communications 672 154 - 160 2023.9 （ ISSN:0006-291X eISSN:1090-2104 ）

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications

Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer with a high mortality rate. Current treatments for PDACs often have side effects, and drug resistance in cancer stem cells (CSCs) would be also a problem. Cyclic guanosine monophosphate (cGMP) suppresses the mitochondrial function of PDACs and inhibits their CSC properties. Metabolic regulation plays a crucial role in the maintenance of CSC phenotype, and we hypothesized that cGMP induction suppresses cancer stem cell properties in the cancer cell through energy-related signaling pathways. We demonstrated that induction of cGMP upregulated the PPARα/PDK4 pathway and suppressed CSC properties in PDAC, and patients with pancreatic cancer with high PDK4 gene expression had a better prognosis than those with low gene expression. Therefore, these mechanisms may provide new therapeutic targets for the eradication of pancreatic CSCs.

DOI： 10.1016/j.bbrc.2023.06.043

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Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1. Reviewed International journal

Kumazoe Motofumi, Ogawa Fumiyo, Hikida Ai, Shimada Yu, Yoshitomi Ren, Watanabe Ryoya, Onda Hiroaki, Fujimura Yoshinori, Tachibana Hirofumi.

Sci Rep 2128 ( 1 ) 2128 - 2128 2023.2 （ ISSN:2045-2322 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Lung fibrosis, including idiopathic pulmonary fibrosis, is an intractable disease accompanied by an irreversible dysfunction in the respiratory system. Its pathogenesis involves the transforming growth factorβ (TGFβ)-induced overproduction of the extracellular matrix from fibroblasts; however, limited countermeasures have been established. In this study, we identified osa-miR172d-5p, a plant-derived microRNA (miR), as a potent anti-fibrotic miR. In silico analysis followed by an in vitro assay based on human lung fibroblasts demonstrated that osa-miR172d-5p suppressed the gene expression of TGF-β activated kinase 1 (MAP3K7) binding protein 1 (Tab1). It also suppressed the TGFβ-induced fibrotic gene expression in human lung fibroblasts. To assess the anti-fibrotic effect of osa-miR172d-5p, we established bleomycin-induced lung fibrosis models to demonstrate that osa-miR172d-5p ameliorated lung fibrosis. Moreover, it suppressed Tab1 expression in the lung tissues of bleomycin-treated mice. In conclusion, osa-miR172d-5p could be a potent candidate for the treatment of lung fibrosis, including idiopathic pulmonary fibrosis.

DOI： 10.1038/s41598-023-29188-6

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Other Link： https://www.nature.com/articles/s41598-023-29188-6
Fustin, a Flavanonol, Synergically Potentiates the Anticancer Effect of Green Tea Catechin Epigallocatechin-3-O-Gallate with Activation of the eNOS/cGMP Axis. Reviewed International journal

Kumazoe Motofumi, Fujimura Yoshinori, Yoshitomi Ren, Shimada Yu, Tachibana Hirofumi.

Journal of agricultural and food chemistry 70 ( 11 ) 3458 - 3466 2022.3 （ ISSN:0021-8561 eISSN:1520-5118 ）

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Epigallocatechin-3-O-gallate (EGCG), a catechin present in green tea, selectively elicits apoptosis in multiple myeloma cells by activating the endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) axis. However, the effects of EGCG alone are limited. Herein, we revealed that fustin, a flavanonol, enhances the EGCG-elicited activation of the cGMP/eNOS axis in multiple myeloma cells. Isobologram analysis demonstrated that EGCG/fustin synergistically elicited cell death in multiple myeloma cells. Importantly, this chemical combination significantly promoted cell death without affecting the normal cells. To assess the effects of EGCG and fustin in vivo, female BALB/c mice were inoculated with multiple myeloma MPC11 cells and then treated with each compound. The combination of EGCG/fustin suppressed tumor growth in vivo without affecting alanine aminotransferase/aspartate aminotransferase levels, the dose-limiting toxicity of EGCG. Consistent with in vitro findings, this combination increased eNOS phosphorylation at Ser1177 in the tumor. Collectively, fustin amplified EGCG-induced activation of the eNOS/cGMP axis.

DOI： 10.1021/acs.jafc.1c07567

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Methylated (-)-epigallocatechin 3-O-gallate potentiates the effect of split vaccine accompanied with upregulation of Toll-like receptor 5. International journal

Kumazoe Motofumi, Takamatsu Kanako, Horie Fuyumi, Yoshitomi Ren, Hamagami Hiroki, Tanaka Hiroshi, Fujimura Yoshinori, Tachibana Hirofumi.

Scientific reports 11 ( 1 ) 23101 - 23101 2021.11

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Glucosyl-hesperidin enhances the cyclic guanosine monophosphate-inducing effect of a green tea polyphenol EGCG.

Kumazoe Motofumi, Tanaka Yasutake, Yoshitomi Ren, Marugame Yuki, Lee Kwan-Woo, Onda Hiroaki, Fujimura Yoshinori , Yonekura Madoka, Shimamoto Yasuyo, Tachibana Hirofumi.

Journal of natural medicines 75 ( 4 ) 1037 - 1042 2021.9

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DOI： 10.1007/s11418-021-01538-6
Time-dependent increase of plasma cGMP concentration followed by oral EGCG administration in mice. Invited Reviewed International journal

Tanaka Yasutake*, Kumazoe Motofumi* (Equal Contribution), Onda Hiroaki, Fujimura Yoshinori, Tachibana Hirofumi.

Food Bioscience 41 101017 - 101017 2021.6

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Language：Japanese Publishing type：Research paper (scientific journal)

DOI： https://doi.org/10.1016/j.fbio.2021.101017
Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation. International journal

Kumazoe Motofumi, Kadomatsu Mai, Bae Jaehoon, Otsuka Yushi, Fujimura Yoshinori, Tachibana Hirofumi.

Molecules (Basel, Switzerland) 25 ( 22 ) 2020.11

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DOI： 10.3390/molecules25225481
Cancer cell selective probe by mimicking EGCG. Reviewed International journal

Kumazoe Motofumi, Hiroi Shun, Tanimoto Yousuke, Miyakawa Jyunichi, Yamanouchi Maasa, Suemasu Yumi, Yoshitomi Ren, Murata Motoki, Fujimura Yoshinori, Takahashi Takashi, Tanaka Hiroshi, Tachibana Hirofumi.

Biochemical and biophysical research communications 525 ( 4 ) 974 - 981 2020.5

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DOI： 10.1016/j.bbrc.2020.03.021
Epigallocatechin-3-O-gallate induces acid sphingomyelinase activation through activation of phospholipase C. International journal

Bae Jaehoon*, Kumazoe Motofumi* (Equal Contribution), Takeuchi Chieri, Hidaka Shiori, Fujimura Yoshinori, Tachibana Hirofumi.

Biochemical and biophysical research communications 520 ( 1 ) 186 - 191 2019.11

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DOI： 10.1016/j.bbrc.2019.09.102
Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression. Reviewed

Kumazoe Motofumi, Yamashita Mai, Nakamura Yuki, Takamatsu Kanako, Bae Jaehoon, Yamashita Shuya, Yamada Shuhei, Onda Hiroaki, Nojiri Takashi, Kangawa Kenji, Tachibana Hirofumi.

JOURNAL OF IMMUNOLOGY 199 ( 9 ) 3261 - 3269 2017.11

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DOI： 10.4049/jimmunol.1601822
SphK1 inhibitor potentiates the anti-cancer effect of EGCG on leukaemia cells. Reviewed

Tsukamoto Shuntaro*, Kumazoe Motofumi* (Equal Contribution), Huang Yuhui, Lesnick Connie, Kay E. Neil, Shanafelt D. Tait, Tachibana Hirofumi.

BRITISH JOURNAL OF HAEMATOLOGY 178 ( 1 ) 155 - 158 2017.7

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DOI： 10.1111/bjh.14119
The FOXO3/PGC-1 beta signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma. Reviewed

Kumazoe Motofumi, Takai Mika, Hiroi Shun, Takeuchi Chieri, Kadomatsu Mai, Nojiri Takashi, Onda Hiroaki, Bae Jaehoon, Huang Yuhui, Takamatsu Kanako, Yamashita Shuya, Kangawa Kenji, Tachibana Hirofumi.

JOURNAL OF BIOLOGICAL CHEMISTRY 292 ( 26 ) 10813 - 10823 2017.6

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DOI： 10.1074/jbc.M116.772111
FOXO3 is essential for CD44 expression in pancreatic cancer cells. Reviewed International journal

Kumazoe Motofumi, Takai Mika, Bae Jaehoon, Hiroi Shun, Huang Yuhui, Takamatsu Kanako, Won Yeong Seon, Yamashita Mai, Hidaka Shiori, Yamashita Shuya, Yamada Shuhei, Murata Motoki, Tsukamoto Shuntaro, Tachibana Hirofumi.

ONCOGENE 36 ( 19 ) 2643 - 2654 2017.5

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DOI： 10.1038/onc.2016.426
PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma. Reviewed

Kumazoe Motofumi, Takai Mika, Hiroi Shun, Takeuchi Chieri, Yamanouchi Maasa, Nojiri Takashi, Onda Hiroaki, Bae Jaehoon, Huang Yuhui, Takamatsu Kanako, Yamashita Shuya, Yamada Shuhei, Kangawa Kenji, Takahashi Takashi, Tanaka Hiroshi, Tachibana Hirofumi.

SCIENTIFIC REPORTS 7 ( 1 ) 1917 2017.5

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DOI： 10.1038/s41598-017-02162-9
Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216. Reviewed

Kumazoe Motofumi, Nakamura Yuki, Yamashita Mai, Suzuki Takashi, Takamatsu Kanako, Huang Yuhui, Bae Jaehoon, Yamashita Shuya, Murata Motoki, Yamada Shuhei, Shinoda Yuki, Yamaguchi Wataru, Toyoda Yui, Tachibana Hirofumi.

JOURNAL OF BIOLOGICAL CHEMISTRY 292 ( 10 ) 4077 - 4088 2017.3

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DOI： 10.1074/jbc.M116.755959
Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells. Reviewed

Huang Yuhui*, Kumazoe Motofumi* (Equal Contribution), Bae Jaehoon, Yamada Shuhei, Takai Mika, Hidaka Shiori, Yamashita Shuya, Kim Yoonhee, Won Yeongseon, Murata Motoki, Tsukamoto Shuntaro, Tachibana Hirofumi.

ONCOLOGY REPORTS 34 ( 3 ) 1162 - 1168 2015.9

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DOI： 10.3892/or.2015.4086
Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells. Reviewed

Kumazoe Motofumi, Fujimura Yoshinori, Hidaka Shiori, Kim Yoonhee, Murayama Kanako, Takai Mika, Huang Yuhui , Yamashita Shuya, Murata Motoki, Miura Daisuke, Wariishi Hiroyuki, Maeda-Yamamoto Mari, Tachibana Hirofumi.

SCIENTIFIC REPORTS 5 2015.3

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/srep09474
Vardenafil, a clinically available phosphodiesterase inhibitor, potentiates the killing effect of EGCG on CLL cells. Reviewed

Kumazoe Motofumi, Tsukamoto Shuntaro, Lesnick Connie, Kay E. Neil, Yamada Koji, Shanafelt D. Tait, Tachibana Hirofumi.

BRITISH JOURNAL OF HAEMATOLOGY 168 ( 4 ) 610 - 613 2015.2

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Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis. Reviewed

Kumazoe Motofumi, Kim Yoonhee, Bae Jaehoon, Takai Mika, Murata Motoki, Suemasu Yumi, Sugihara Kaori, Yamashita Shuya, Tsukamoto Shuntaro, Huang Yuhui, Nakahara Kanami, Yamada Koji, Tachibana Hirofumi.

FEBS LETTERS 587 ( 18 ) 3052 - 3057 2013.9

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DOI： 10.1016/j.febslet.2013.07.041
67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis. Reviewed

Kumazoe Motofumi, Sugihara Kaori, Tsukamoto Shuntaro, Huang Yuhui, Tsurudome Yukari, Suzuki Takashi, Suemasu Yumi, Ueda Naoki, Yamashita Shuya, Kim Yoonhee, Yamada Koji, Tachibana Hirofumi.

JOURNAL OF CLINICAL INVESTIGATION 123 ( 2 ) 787 - 799 2013.2

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DOI： 10.1172/JCI64768
Phosphodiesterase 5 Inhibitor Potentiates Epigallocatechin 3-O-Gallate-Induced Apoptotic Cell Death via Activation of the cGMP Signaling Pathway in Caco-2 Cells

Bae, J; Lee, K; Park, JS; Jung, J; Tachibana, H; Fujimura, Y; Kumazoe, M; Lim, JS; Cho, YC; Lee, SJ; Park, SJ

CURRENT ISSUES IN MOLECULAR BIOLOGY 44 ( 12 ) 6247 - 6256 2022.12 （ ISSN:1467-3037 eISSN:1467-3045 ）

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Language：English Publisher：Current Issues in Molecular Biology

Epigallocatechin 3-O-gallate (EGCG) is a predominant component in green tea with various health benefits. The 67 kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that is overexpressed in various types of cancer; 67LR was identified a cell surface EGCG target that plays a pivotal role in tumor growth, metastasis, and resistance to chemotherapy. However, the plasma concentration of EGCG is limited, and its molecular mechanisms remain unelucidated in colon cancer. In this study, we found that the phosphodiesterase 5 (PDE5) inhibitor, vardenafil (VDN), potentiates EGCG-induced apoptotic cell death in colon cancer cells. The combination of EGCG and VDN induced apoptosis via activation of the endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase Cδ signaling pathway. In conclusion, the PDE5 inhibitor, VDN, may reduce the intracellular PDE5 enzyme activity that potentiates EGCG-induced apoptotic cell death in Caco-2 cells. These results suggest that PDE5 inhibitors can be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. Therefore, EGCG may be employed as a therapeutic candidate for colon cancer.

DOI： 10.3390/cimb44120426

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Myricetin improves cognitive function in SAMP8 mice and upregulates brain-derived neurotrophic factor and nerve growth factor. International journal

Shimada Yu, Sato Yuka, Kumazoe Motofumi, Kitamura Ryo, Fujimura Yoshinori, Tachibana Hirofumi.

Biochemical and biophysical research communications 616 33 - 40 2022.8 （ ISSN:0006-291X eISSN:1090-2104 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Biochemical and Biophysical Research Communications

Introduction: Considering that neurodegeneration is an irreversible process, an efficient, low-burden approach to prevent dementia is strongly needed. Here, we show that the daily intake of myricetin normalised cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8) mice. Methods: SAMP8 mice were fed a diet supplemented with myricetin and novel object recognition tests and Y-maze tests were performed. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in brains of SAMP8 mice were measured. The phosphorylation level of cAMP-response-element-binding protein (CREB) level in brains of SAMP8 mice were evaluated. Also, SH-SY5Y cells were treated with myricetin and cAMP levels were measured. Results: In SAMP8 mice, neurotrophins, including BDNF and NGF, were downregulated relative to levels in their normal counterparts. In addition, myricetin intake upregulated the phosphorylation of CREB, the major transcription factor for BDNF and NGF. Also, myricetin induced cAMP upregulation, and CREB phosphorylation via a cAMP-dependent protein kinase-dependent manner in SH-SY5Y cells. Conclusion: Taken together, myricetin improves cognitive function in SAMP8 mice and upregulates BDNF and NGF.

DOI： 10.1016/j.bbrc.2022.05.039

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Metabolic Profiling for Evaluating the Dipeptidyl Peptidase-IV Inhibitory Potency of Diverse Green Tea Cultivars and Determining Bioactivity-Related Ingredients and Combinations. International journal

Fujimura Yoshinori, Watanabe Mototsugu, Morikawa-Ichinose Tomomi, Fujino Konatsu, Yamamoto Mao, Nishioka Seita, Inoue Chihiro, Ogawa Fumiyo, Yonekura Madoka, Nakasone Akari, Kumazoe Motofumi, Tachibana Hirofumi.

Journal of agricultural and food chemistry 70 ( 21 ) 6455 - 6466 2022.6 （ ISSN:0021-8561 eISSN:1520-5118 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Agricultural and Food Chemistry

There are numerous cultivars of tea (Camellia sinensis L.), but the differences in their anti-hyperglycemic-related effects are largely unknown. The inhibition of the dipeptidyl peptidase (DPP)-IV enzyme plays an essential role in controlling hyperglycemia in diabetes by blocking the degradation of incretin hormones, which is necessary for insulin secretion. In this study, we examined the DPP-IV inhibitory activity of leaf extracts from diverse Japanese green tea cultivars. The inhibitory rates differed among tea extracts. Metabolic profiling (MP), using liquid chromatography-mass spectrometry, of all cultivars revealed compositional differences among cultivars according to their DPP-IV inhibitory capacity. Epigallocatechin-3-O-(3-O-methyl)gallate, kaempferol-3-O-rutinoside, myricetin-3-O-glucoside/galactoside, and theogallin were newly identified as DPP-IV inhibitors. The bioactivity of a tea extract was potentiated by adding these ingredients in combination. Our results show that MP is a useful approach for evaluating the DPP-IV inhibitory potency of green tea and for determining bioactivity-related ingredients and combinations.

DOI： 10.1021/acs.jafc.2c01693

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Soy isoflavone metabolite equol inhibits cancer cell proliferation in a PAP associated domain containing 5-dependent and an estrogen receptor-independent manner. International journal

Yamashita Shuya, Lin Ichian, Oka Chihiro, Kumazoe Motofumi, Komatsu Satomi, Murata Motoki, Kamachi Shoko, Tachibana Hirofumi.

The Journal of nutritional biochemistry 100 108910 - 108910 2022.2 （ ISSN:0955-2863 eISSN:1873-4847 ）

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Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Nutritional Biochemistry

Isoflavone is a species of polyphenol found mainly in soy and soy products. Many studies have demonstrated its estrogen receptor (ER)-dependent action. Equol is an intestinal metabolite of a major soy isoflavone daidzein. We aimed to elucidate the mechanism for ER-independent actions of equol. Equol has been shown to inhibit proliferation of HeLa human cervical cancer cells and mouse melanoma B16 cells in an ER-independent manner. Using functional genetic screening, PAP associated domain containing 5 (PAPD5), which is a non-canonical poly(A) polymerase, was identified as an essential molecule in the ER-independent action. While peroral administration of equol inhibited tumor growth of control B16 cells subcutaneously inoculated in mice, it had little effect on the growth of PAPD5-ablated B16 cells. Intriguingly, equol progressed tumor growth of the PAPD5-ablated human breast cancer MCF-7 cells, which have high ERα expression. Equol has been found to induce polyadenylation of snoRNAs in a PAPD5-depdendent manner. Furthermore, peroral equol administration increased microRNA miR-320a expression in tumors. Together, these results suggest that equol may have a dual effect on ER-positive cancer cells, acting with, antiproliferative activity through PAPD5 and exhibiting proliferative activity via ERα and the former could be associated with miR-320a.

DOI： 10.1016/j.jnutbio.2021.108910

Web of Science

Scopus

PubMed
Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p

MARUGAME Yuki, TAKESHITA Natsuko, YAMADA Shuhei, YOSHITOMI Ren, KUMAZOE Motofumi, FUJIMURA Yoshinori, TACHIBANA Hirofumi

Bioscience of Microbiota, Food and Health 41 ( 2 ) 66 - 72 2022 （ ISSN:2186-6953 eISSN:21863342 ）

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Language：English Publisher：BMFH Press

<p>Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer’s disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin=1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.</p>

DOI： 10.12938/bmfh.2021-067

Web of Science

Scopus

PubMed

CiNii Research
The combined effect of green tea and α-glucosyl hesperidin in preventing obesity: a randomized placebo-controlled clinical trial. International journal

Yoshitomi Ren, Yamamoto Mao, Kumazoe Motofumi, Fujimura Yoshinori, Yonekura Madoka, Shimamoto Yasuyo, Nakasone Akari, Kondo Satoshi, Hattori Hiroki, Haseda Akane, Nishihira Jun, Tachibana Hirofumi.

Scientific reports 11 ( 1 ) 19067 - 19067 2021.9

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/s41598-021-98612-6
Eriodictyol-Amplified 67-kDa Laminin Receptor Signaling Potentiates the Antiallergic Effect of O-Methylated Catechin. International journal

Fujimura Yoshinori, Fujino Konatsu, Yoshimoto Takanori, Nezu Ayaka, Marugame Yuki, Bae Jaehoon, Kumazoe Motofumi, Tachibana Hirofumi.

Journal of natural products 84 ( 6 ) 1823 - 1830 2021.6

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/acs.jnatprod.1c00337
Plasma Homocysteine Concentration is Associated with the Expression Level of Folate Receptor 3. Reviewed International journal

Yoshitomi Ren, Nakayama Kai, Yamashita Shuya, Kumazoe Motofumi, Lin Ting-An, Mei Chen-Yi, Marugame Yuki, Fujimura Yoshinori, Maeda-Yamamoto Mari, Kuriyama Shinichi, Tachibana Hirofumi.

Scientific Reports 10 ( 1 ) 10283 - 10283 2020.12

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DOI： 10.1038/s41598-020-67288-9
EGCG down-regulates MuRF1 expression through 67-kDa laminin receptor and the receptor signaling is amplified by eriodictyol. Reviewed

Murata Motoki, Shimizu Yuki, Marugame Yuki, Nezu Ayaka, Fujino Konatsu, Yamada Shuhei, Kumazoe Motofumi, Fujimura Yoshinori, Tachibana Hirofumi.

Journal of natural medicines 2020.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/s11418-020-01417-6
Procyanidin C1 Inhibits Melanoma Cell Growth by Activating 67-kDa Laminin Receptor Signaling. International journal

Bae Jaehoon, Kumazoe Motofumi, Murata Kyosuke, Fujimura Yoshinori, Tachibana Hirofumi.

Molecular nutrition & food research 64 ( 7 ) e1900986 2020.4

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1002/mnfr.201900986
Diallyl disulfide potentiates anti-obesity effect of green tea in high-fat/high-sucrose diet-induced obesity. International journal

Bae Jaehoon, Kumazoe Motofumi, Fujimura Yoshinori, Tachibana Hirofumi.

The Journal of nutritional biochemistry 64 152 - 161 2019.2

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jnutbio.2018.10.014
Alteration of specific cytokine expression patterns in patients with breast cancer. International journal

Kawaguchi Kosuke, Sakurai Masashi, Yamamoto Yasuko, Suzuki Eiji, Tsuda Moe, Kataoka R Tatsuki, Hirata Masahiro, Nishie Mariko, Nojiri Takashi, Kumazoe Motofumi, Saito Kuniaki, Toi Masakazu.

Scientific reports 9 ( 1 ) 2924 - 2924 2019.2

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/s41598-019-39476-9
Saturated fatty acid attenuates anti-obesity effect of green tea. Reviewed

Yamashita Shuya, Hirashima Asami, Lin I-Chian, Bae Jaehoon, Nakahara Kanami, Murata Motoki, Yamada Shuhei , Kumazoe Motofumi, Yoshitomi Ren, Kadomatsu Mai, Sato Yuka, Nezu Ayaka, Hikida Ai, Fujino Konatsu, Murata Kyosuke , Maeda-Yamamoto Mari, Tachibana Hirofumi.

Scientific Reports 8 ( 1 ) 10023 2018.7

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Hydrogen sulphide donors selectively potentiate a green tea polyphenol EGCG-induced apoptosis of multiple myeloma cells. Reviewed International journal

Bae Jaehoon, Kumazoe Motofumi, Yamashita Shuya, Tachibana Hirofumi.

SCIENTIFIC REPORTS 7 ( 1 ) 6665 - 6665 2017.7

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/s41598-017-06879-5
Oligomer formation of a tea polyphenol, EGCG, on its sensing molecule 67 kDa laminin receptor. Reviewed

Huang Yuhui, Sumida Mami, Kumazoe Motofumi, Sugihara Kaori, Suemasu Yumi, Yamada Shuhei, Yamashita Shuya, Miyakawa Jyunichi, Takahashi Takashi, Tanaka Hiroshi, Fujimura Yoshinori, Tachibana Hirofumi.

CHEMICAL COMMUNICATIONS 53 ( 12 ) 1941 - 1944 2017.2

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1039/c6cc09504f
Green tea cultivar 'Benifuuki' potentiates split vaccine-induced immunoglobulin A production. Reviewed

Won Yeong-Seon, Kumazoe Motofumi, Takamatsu Kanako, Shinoda Yuki, Sonoda Saki, Okada Kenji, Okamoto Takehisa, Tachibana Hirofumi.

JOURNAL OF NATURAL MEDICINES 71 ( 1 ) 68 - 75 2017.1

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/s11418-016-1028-7
The Synthesis of trans-Flavan-3-ol Gallates by Regioselective Oxidative Etherification and Their Cytotoxicity Mediated by 67LR. Reviewed

Shiraishi Nana, Kumazoe Motofumi, Fuse Shinichiro, Tachibana Hirofumi, Tanaka Hiroshi.

CHEMISTRY-A EUROPEAN JOURNAL 22 ( 37 ) 13050 - 13053 2016.9

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1002/chem.201602817
6-Azido-6-deoxy-L-idose as a Hetero-Bifunctional Spacer for the Synthesis of Azido-Containing Chemical Probes. Reviewed

Hamagami Hiroki, Kumazoe Motofumi, Yamaguchi Yoshiki, Fuse Shinichiro, Tachibana Hirofumi, Tanaka Hiroshi.

CHEMISTRY-A EUROPEAN JOURNAL 22 ( 36 ) 12884 - 12890 2016.8

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1002/chem.201602044
The Combination of Green Tea Extract and Eriodictyol Inhibited High-Fat/High-Sucrose Diet-Induced Cholesterol Upregulation Is Accompanied by Suppression of Cholesterol Synthesis Enzymes. Reviewed

Yamashita Mai, Kumazoe Motofumi, Nakamura Yuki, Won Yeong Seon, Bae Jaehoon, Yamashita Shuya, Tachibana Hirofumi.

JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 62 ( 4 ) 249 - 256 2016.8

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3177/jnsv.62.249
Equol suppresses inflammatory response and bone erosion due to rheumatoid arthritis in mice. Reviewed

Lin I-Chian, Yamashita Shuya, Murata Motoki, Kumazoe Motofumi, Tachibana Hirofumi.

JOURNAL OF NUTRITIONAL BIOCHEMISTRY 32 101 - 106 2016.6

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.jnutbio.2016.02.012
Green Tea Catechin Metabolites Exert Immunoregulatory Effects on CD4(+) T Cell and Natural Killer Cell Activities. Reviewed

Kim Yoon Hee, Won Yeong-Seon, Yang Xue, Kumazoe Motofumi, Yamashita Shuya, Hara Aya, Takagaki Akiko, Goto Keiichi, Nanjo Fumio, Tachibana Hirofumi.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 64 ( 18 ) 3591 - 3597 2016.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/acs.jafc.6b01115
gamma-Tocotrienol upregulates aryl hydrocarbon receptor expression and enhances the anticancer effect of baicalein. Reviewed

Yamashita Shuya, Baba Kiwako, Makio Akiko, Kumazoe Motofumi, Huang Yuhui, Lin I-Chian, Bae Jaehoon, Murata Motoki, Yamada Shuhei, Tachibana Hirofumi.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 473 ( 4 ) 801 - 807 2016.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.bbrc.2016.03.111
Epigallocatechin-3-O-gallate up-regulates microRNA-let-7b expression by activating 67-kDa laminin receptor signaling in melanoma cells. Reviewed

Yamada Shuhei, Tsukamoto Shuntaro, Huang Yuhui, Makio Akiko, Kumazoe Motofumi, Yamashita Shuya, Tachibana Hirofumi.

SCIENTIFIC REPORTS 6 19225 2016.1

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/srep19225
Sphingosine Kinase-1 Protects Multiple Myeloma from Apoptosis Driven by Cancer-Specific Inhibition of RTKs. Reviewed

Tsukamoto Shuntaro, Huang Yuhui, Kumazoe Motofumi, Lesnick Connie, Yamada Shuhei, Ueda Naoki, Suzuki Takashi, Yamashita Shuya, Kim Yoon Hee, Fujimura Yoshinori, Miura Daisuke, Kay E. Neil, Shanafelt D. Tait, Tachibana Hirofumi.

MOLECULAR CANCER THERAPEUTICS 14 ( 10 ) 2303 - 2312 2015.10

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1158/1535-7163.MCT-15-0185
1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose increases a population of T regulatory cells and inhibits IgE production in ovalbumin-sensitized mice. Reviewed

Kim Y.H, Yang X, Yamashita S, Kumazoe M, Huang Y, Nakahara K, Won Y.S, Murata M, Lin I.-C, Tachibana H

International Immunopharmacology 26 ( 1 ) 30 - 36 2015.5

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.intimp.2015.02.025
67-kDa Laminin Receptor-dependent Protein Phosphatase 2A (PP2A) Activation Elicits Melanoma-specific Antitumor Activity Overcoming Drug Resistance. Reviewed

Tsukamoto Shuntaro, Huang Yuhui, Umeda Daisuke, Yamada Shuhei, Yamashita Shuya, Kumazoe Motofumi, Kim Yoonhee, Murata Motoki, Yamada Koji, Tachibana Hirofumi.

JOURNAL OF BIOLOGICAL CHEMISTRY 289 ( 47 ) 32671 - 32681 2014.11

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1074/jbc.M114.604983
IL-4 receptor α in non-lipid rafts is the target molecule of strictinin in inhibiting STAT6 activation. Reviewed

Kim Yoonhee, Ninomiya Yu, Yamashita Shuya, Kumazoe Motofumi, Huang Yuhui, Nakahara Kanami, Won Yeong Seon, Murata Motoki, Fujimura Yoshinori, Yamada Koji, Tachibana Hirofumi.

Biochemical and Biophysical Research Communications 450 ( 1 ) 824 - 830 2014.7

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.bbrc.2014.06.069
Green Tea Extract Containing a Highly Absorbent Catechin Prevents Diet-Induced Lipid Metabolism Disorder. Reviewed

Takashi Suzuki, Motofumi Kumazoe, Yoonhee Kim, Shuya Yamashita, Kanami Nakahara, Shuntaro Tsukamoto, Masako Sasaki, Takatoki Hagihara, Yukari Tsurudome, Yuhui Huang, Mari Maeda-Yamamoto, Yuki Shinoda, Wataru Yamaguchi, Koji Yamada, Hirofumi Tachibana.

SCIENTIFIC REPORTS 3 2013.9

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/srep02749
Anti-Cancer Effect of Water Extracts Prepared from Chrysanthemum Flowers and Leaves Shiranui Himekiku Invited Reviewed

Murayama Kanako, Sawa Tomoko, Koga Hiroaki, Yamaguchi Satoshi, Kumazoe Motofumi, Otsuka Takafumi, Miyazaki Yoshiyuki, Tachibana Hirofumi, Koji Yamada.

Nippon Shokuhin Kagaku Kogaku Kaishi 60 ( 2 ) 80 - 86 2013.2

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Oxygen partial pressure modulates 67-kDa laminin receptor expression, leading to altered activity of the green tea polyphenol, EGCG. Reviewed

Tsukamoto Shuntaro, Yamashita Shuya, Kim Yoon Hee, Kumazoe Motofumi, Huang Yuhui, Yamada Koji, Tachibana Hirofumi.

FEBS LETTERS 586 ( 19 ) 3441 - 3447 2012.9

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DOI： 10.1016/j.febslet.2012.07.065
Isoflavones suppress the expression of the FcεRI high-affinity immunoglobulin receptor independent of the estrogen receptor. Reviewed

Yamashita Shuya, Tsukamoto Shuntaro, Kumazoe Motofumi, Kim Yoon Hee, Yamada Koji, Tachibana Hirofumi.

Journal of Agricultural and Food Chemistry 60 ( 34 ) 8379 - 8385 2012.8

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1021/jf301759s
Green tea polyphenol EGCG induces lipid-raft clustering and apoptotic cell death by activating protein kinase Cδ and acid sphingomyelinase through a 67 kDa laminin receptor in multiple myeloma cells. Reviewed

Tsukamoto Shuntraro, Hirotsu Keisuke, Kumazoe Motofumi, Goto Yoko, Sugihara Kaori, Suda Takashi, Tsurudome Yukari, Suzuki Takashi, Yamashita Shuya, Kim Yoonhee, Huang Yuhui, Yamada Koji, Tachibana Hirofumi.

Biochemical Journal 443 ( 2 ) 525 - 534 2012.4

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1042/BJ20111837
Anti-Allergic Effects of Kakrol (Momordica dioica Roxb.) Flesh Extract. Reviewed

Kim Yoon Hee, Ida Megumi, Yamashita Shuya, Tsukamoto Shuntaro, Kumazoe Motofumi, Sumida Mami, Kawakami Mitsuo, Yamada Koji, Tachibana Hirofumi.

Bioscience of Microbiota, Food and Healt 31 ( 1 ) 1 - 6 2012.1

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.12938/bmfh.31.1
Vitamin A Enhances Antitumor Effect of a Green Tea Polyphenol on Melanoma by Upregulating the Polyphenol Sensing Molecule 67-kDa Laminin Receptor. Reviewed

Lee Ju Hye, Kishikawa Mutsumi, Kumazoe Motofumi, Yamada Koji, Tachibana Hirofumi.

PLOS ONE 5 ( 6 ) 2010.6

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DOI： 10.1371/journal.pone.0011051

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Books

緑茶の機能性と薬理緑茶カテキンセンシングと機能性増強技術

藤村由紀, 熊添基文, 立花宏文（Role：Joint author）

機能性食品と薬理栄養 2019.8

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Language：Japanese Book type：Scholarly book
茶カテキンの活性発現機序に基づいた新たながん治療戦略

熊添基文, 立花宏文（Role：Joint author）

バイオサイエンスとインダストリー 2018.11

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Language：Japanese Book type：Scholarly book
個人に適した効果的な摂取条件等を特定する手法の開発及び摂取条件等を普及するためのモデル体制の構築(茶)第1章緑茶の機能性感知調節作用の研究開発

立花宏文, 山下修矢, 熊添基文（Role：Joint author）

農林水産省農林水産技術会議事務局研究成果 (農林水産技術会議事務局研究成果) 2015.2

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Responsible for pages：J-GLOBAL ID：201502257943898251 Language：Japanese Book type：Scholarly book

Presentations

メチル化EGCGによるスプリット型ワクチンの作用増強

熊添基文，高松香菜子, 藤村由紀, 立花宏文

2021年度西日本・中四国・関西支部合同大会 2021.9

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Event date： 2021.9

Language：Japanese Presentation type：Oral presentation (general)

Venue：福岡 Country：Japan
Epigallocatechin-3-O-gallate(EGCG)/Phosphodiesterase3阻害剤併用は膵臓がんのがん幹細胞性を阻害する

熊添基文, 高井美佳, 廣井舜, 高松香菜子, 門松舞, 山下麻衣, 藤村由紀, 立花宏文

日本農芸化学会 2020年度大会 2020.3

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Event date： 2020.3

Language：Japanese Presentation type：Oral presentation (general)

Venue：福岡 Country：Japan
cGMP mediates beneficial effect of EGCG. Invited International conference

Kumazoe M, Yoshinori F, Tachibana H.

International Conference on Food Factors 2019.11

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Event date： 2019.11

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Kobe Country：Japan
EGCG induces cancer-specific cell death via the sensing receptor-mediated cGMP production. Invited International conference

Kumazoe M, Tachibana H.

Functional and Medical Foods, Bioactive Compounds and Biomarkers 2015.11

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Event date： 2015.11

Language：Japanese Presentation type：Symposium, workshop panel (public)

Venue：Kobe Country：Japan
EGCG induces cancer-specific cell death via the sensing receptor-mediated cGMP production. Invited International conference

Kumazoe M, Tachibana H.

International Conference on Tea. 2013.12

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Event date： 2013.12

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Shizuoka Country：Japan
67-kDa laminin receptor and cGMP induced cancer-selective apoptosis. Invited International conference

Kumazoe M, Tachibana H.

The 6th International Meeting on cGMP 2013.6

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Event date： 2013.6

Language：English Presentation type：Symposium, workshop panel (public)

Venue：Erfurt Country：Germany
食品機能性を担う細胞外小胞とマイクロ RNA Invited

熊添基文, 立花宏文

第78回日本栄養・食糧学会大会 2024.5

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Language：Japanese Presentation type：Symposium, workshop panel (public)

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microRNA as a Food Function Mediator Invited

熊添基文, 立花宏文

2024 年度日本農芸化学会東京大会 BBB 連携シンポジウム 2024.3

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Language：Japanese Presentation type：Symposium, workshop panel (public)

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緑茶ポリフェノールEGCGのcGMPを介した生理作用 Invited

熊添基文, 藤村由紀, 立花宏文

生物機能研究会2024宮崎大会 2024.7

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Language：Japanese Presentation type：Symposium, workshop panel (public)

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緑茶カテキンのケミカルバイオロジー Invited

熊添基文, 藤村由紀, 立花宏文

第十七回ポリフェノール学会学術集会 2024.8

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Language：Japanese Presentation type：Symposium, workshop panel (nominated)

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MISC

67-kDa Laminin Receptor Mediates the Beneficial Effects of Green Tea Polyphenol EGCG Reviewed

Motofumi Kumazoe, Yoshinori Fujimura, Hirofumi Tachibana

Current Pharmacology Reports 2020.1

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Language：English Publishing type：Article, review, commentary, editorial, etc. (scientific journal)

DOI： https://doi.org/10.1007/s40495-020-00228-3
緑茶カテキンセンシング機構とその応用展開-カテキンパワーの引き出し方. Reviewed

熊添基文, 立花宏文

化学と生物 2016.3

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Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)

Industrial property rights

Patent	Number of applications: 1	Number of registrations: 0
Utility model	Number of applications: 0	Number of registrations: 0
Design	Number of applications: 0	Number of registrations: 0
Trademark	Number of applications: 0	Number of registrations: 0

Professional Memberships

日本農芸化学会
日本栄養・食糧学会

Academic Activities

座長

日本農芸化学会中四国・西日本支部2023年度合同大会（ Japan ） 2023.9

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Type：Competition, symposium, etc.

Research Projects

Anti-fibrotic effect of microRNAs in NASH models

Grant number：24K08835 2024.4 - 2027.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

熊添基文, 藤村由紀

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Grant type：Scientific research funding

肺、肝臓、腎臓の線維化は治療困難である。現状、線維化疾患に対する有効な創薬は乏しく、予後の大幅な改善には至っていない。
これに対して、申請者は大豆イソフラボンの代謝物である Equol が顕著な抗線維化作用を発揮するという発見をもとに、その仕組みを解明してつつある。本研究は安全なポリフェノールの抗線維化作用解明を通じて、新たな治療標的の探索を目指す。

CiNii Research
血管内皮細胞を起点とする抗炎症機構の解明

Grant number：20K05960 2020 - 2022

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
血管内皮細胞を起点とする抗炎症機構の解明

Grant number：20K05960 2020 - 2022

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Principal investigator Grant type：Scientific research funding
cGMPの生体調節作用

2018.4 - 2022.6

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Authorship：Principal investigator

We have been investigated the signaling pathway of cGMP-elicited beneficial effects.
ANPの組織繊維化抑制作用の機序解明と肺線維症治療への応用

Grant number：18K06909 2018 - 2020

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

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Authorship：Coinvestigator(s) Grant type：Scientific research funding
cGMP の癌幹細胞抑制作用の機構解明

Grant number：18K14442 2018 - 2019

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Early-Career Scientists

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Authorship：Principal investigator Grant type：Scientific research funding
小児がんに関する研究 (具体的内容は非公開)

2017 - 2019

がんの子供を守る会

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Authorship：Principal investigator Grant type：Contract research
癌幹細胞に対する直ちに臨床応用可能な治療戦略の確立

2017 - 2018

興和生命科学振興財団

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Authorship：Principal investigator Grant type：Contract research
cGMP の抗がん作用機構の解明と臨床応用への基盤確立

2017 - 2018

武田科学振興財団

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Authorship：Principal investigator Grant type：Contract research
天然物の作用機構解明に基づく新規がん細胞致死機構の探索

Grant number：15K18821 2015 - 2017

Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

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Authorship：Principal investigator Grant type：Scientific research funding
食品因子センシング調節を介した食品間の機能的相互作用の解明

Grant number：15K16231 2015 - 2016

Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

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Authorship：Collaborating Investigator(s) (not designated on Grant-in-Aid) Grant type：Scientific research funding
緑茶カテキンＥＧＣＧをリード化合物とするがん幹細胞を殺傷する新規化合物の作製　（日本学術振興会PD）

Grant number：14J30004 2014 - 2016

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows

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Authorship：Principal investigator Grant type：Scientific research funding
ＥＧＣＧのプローブ化によるがん医療への応用 (日本学術振興会DC1)

Grant number：11J01339 2011 - 2013

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows

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Authorship：Principal investigator Grant type：Scientific research funding

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Class subject

食糧化学実験

2023.4 - 2023.9 First semester
微生物学基礎実験

2022.10 - 2023.3 Second semester
食糧化学実験

2022.4 - 2022.9 First semester

Media Coverage

柑橘ポリフェノールと緑茶ポリフェノール併用により顕著な抗肥満作用を発揮することをヒト臨床試験により確認した

マイナビnニュース 2021.10

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柑橘ポリフェノールと緑茶ポリフェノール併用により顕著な抗肥満作用を発揮することをヒト臨床試験により確認した
緑茶とみかんの成分　抗アレルギー相乗効果 Newspaper, magazine

日本経済新聞 2018.4

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緑茶とみかんの成分　抗アレルギー相乗効果
九大、膵臓がん幹細胞の生存・転移に重要なしくみを攻撃する化合物を発見 Newspaper, magazine

日本経済新聞 2017.5

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九大、膵臓がん幹細胞の生存・
転移に重要なしくみを攻撃する化合物を発見
緑茶の作用を強める組み合わせ Newspaper, magazine

朝日新聞 2013.1

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緑茶の作用を強める組み合わせ