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Molecular-Targeting Prevention

Subject Molecular-Targeting Prevention
Michihiro Mutoh
Associate Professor: Yoshihiro Sowa
Lecturer: Motoki Watanabe
Assistant Professor: osuke Iizumi
Assistant Professor: Mitsuharu Masuda
Research Contents

Cancer chemoprevention trial of cancer high-risk group aimed for clinical application


Development of a novel examination and treatment for precancerous lesion, or novel cancer prevention methods, based on regulation of gene expression

Development of prevention methods to prevent cancer with the aim of reducing side effects, and increasing interaction / sensitivity / overcoming drug resistance through combination of molecular target, detected from risk factors and molecular mechanisms


Development of prevention methods using drug repositioning and functional foods through industry-academia collaboration

Elucidation of the mechanism of natural products for cancer prevention using chemo-proteomics and chemo-informatics, and resultant application to in silico screening

Development of a novel cancer prevention method focusing on cancer-specific metabolic disorders

Search for anticancer substances focusing on metabolic changes through a gene mutation, and its in vivo evaluation

Identification of target proteins for cancer chemopreventive agents and functional food components using techniques of chemical biology, and precise analysis of its mechanisms


Dissemination and implementation (D & I) research regarding cancer prevention



Histone deacetylase inhibitor OBP-801 and amrubicin synergistically inhibit the growth of squamous cell lung carcinoma by inducing mitochondrial ASK1-dependent apoptosis.
Chihara Y, Iizumi Y*, Horinaka M, Watanabe M, Goi W, Morita M, Nishimoto E, Sowa Y, Yamada T, Takayama K, Sakai T.
Int J Oncol. 2020; 56: 848-56.

Utility of mesalazine in familial adenomatous polyposis: Clinical report of reduction of polyp size in patients with ulcerative colitis, and safety examination in familial adenomatous polyposis patients.
Ishikawa H, Mutoh M*, Abe T, Nakajima T, Takeuchi Y, Ezoe Y, Wakabayashi K, Doyama H, Sakai T.
Pharmacology. 2019; 104(1-2): 51-56.
Higher enterococcus counts indicate a lower risk of colorectal adenomas: a prospective cohort study.
Kawano A, Ishikawa H, Mutoh M*, Kubota H, Matsuda K, Tsuji H, Matsumoto K, Nomoto K, Tanaka R, Nakamura T, Wakabayashi K, Sakai T.
Oncotarget. 2018; 9: 21459-67.
The histone deacetylase inhibitor OBP-801 and eribulin synergistically inhibit the growth of triple-negative breast cancer cells with the suppression of survivin, Bcl-xL, and the MAPK pathway.
Ono H, Sowa Y*, Horinaka M, Iizumi Y, Watanabe M, Morita M, Nishimoto E, Taguchi T, Sakai T.
Breast Cancer Res Treat. 2018; 171: 43-52.
Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma.
Hagiwara N, Watanabe M*, Iizuka-Ohashi M, Yokota I, Toriyama S, Sukeno M, Tomosugi M, Sowa Y, Hongo F, Mikami K, Soh J, Fujito A, Miyashita H, Morioka Y, Miki T, Ukimura O, Sakai T.
Cancer Lett. 2018; 431: 182-9.
Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells.
Iizuka-Ohashi M, Watanabe M*, Sukeno M, Morita M, Hoang NTH, Kuchimaru T, Kizaka-Kondoh S, Sowa Y, Sakaguchi K, Taguchi T, Sakai T.
Oncotarget. 2018; 9: 19597-612.
Ribosomal protein S3 regulates XIAP expression independently of the NF-κB pathway in breast cancer cells.
Ono H, Iizumi Y*, Goi W, Sowa Y, Taguchi T, Sakai T.
Oncol Rep. 2017; 38: 3205-10.
The pleiotropic regulation of cyclin D1 by newly identified sesaminol-binding protein ANT2.
Watanabe M*, Iizumi Y, Sukeno M, Iizuka-Ohashi M, Sowa Y, Sakai T.
Oncogenesis. 2017; 6: e311.
Three combined treatments, a novel HDAC inhibitor OBP-801/YM753, 5-fluorouracil, and paclitaxel, induce G₂ phase arrest through the p38 pathway in human ovarian cancer cells.
Akiyama M, Sowa Y*, Taniguchi T, Watanabe M, Yogosawa S, Kitawaki J, Sakai T.
Oncol Res. 2017; 25: 1245-52.
Endoscopic management of familial adenomatous polyposis in patients refusing colectomy.
Ishikawa H, Mutoh M*, Iwama T, Suzuki S, Abe T, Takeuchi Y, Nakamura T, Ezoe Y, Fujii G, Wakabayashi K, Nakajima T, Sakai T.
Endoscopy. 2016; 48(1): 51-5.
Resveratrol directly targets DDX5 resulting in suppression of the mTORC1 pathway in prostate cancer.
Taniguchi T, Iizumi Y*, Watanabe M, Masuda M, Morita M, Aono Y, Toriyama S, Oishi M, Goi W, Sakai T.
Cell Death Dis. 2016; 7: e2211.
Phosphorylated retinoblastoma protein is a potential predictive marker of irinotecan efficacy for colorectal cancer.
Ikai A, Watanabe M, Sowa Y*, Kishimoto M, Yanagisawa A, Fujiwara H, Otsuji E, Sakai T.
Int J Oncol. 2016; 48: 1297-304.
Resibufogenin induces G1-phase arrest through the proteasomal degradation of cyclin D1 in human malignant tumor cells.
Ichikawa M, Sowa Y*, Iizumi Y, Aono Y, Sakai T.
PLoS One. 2015; 10: e0129851.
The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial.
Ishikawa H, Mutoh M*, Suzuki S, Tokudome S, Saida Y, Abe T, Okamura S, Tajika M, Joh T, Tanaka S, Kudo SE, Matsuda T, Iimuro M, Yukawa T, Takayama T, Sato Y, Lee K, Kitamura S, Mizuno M, Sano Y, Gondo N, Sugimoto K, Kusunoki M, Goto C, Matsuura N, Sakai T, Wakabayashi K.
Gut. 2014 ; 63(11): 1755-9. 
The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells.
Furutani A, Sowa Y*, Fujiwara H, Otsuji E, Sakai T.
Oncol Res. 2014; 21: 281-6.
Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial.
Ishikawa H*, Wakabayashi K, Suzuki S, Mutoh M, Hirata K, Nakamura T, Takeyama I, Kawano A, Gondo N, Abe T, Tokudome S, Goto C, Matsuura N, Sakai T.
Cancer Med. 2013; 2: 50-6.
The flavonoid apigenin downregulates CDK1 by directly targeting ribosomal protein S9.
Iizumi Y, Oishi M, Taniguchi T, Goi W, Sowa Y, Sakai T.
PLoS One. 2013; 8: e73219.
Apigenin sensitizes prostate cancer cells to Apo2L/TRAIL by targeting adenine nucleotide translocase-2.
Oishi M, Iizumi Y, Taniguchi T, Goi W, Miki T, Sakai T.
PLoS One. 2013; 8: e55922.
Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells.
Watanabe M, Sowa Y*, Yogosawa M, Sakai T.
Cancer Sci. 2013; 104: 687-93.
Retinoblastoma gene-independent G1 phase arrest by flavone, phosphatidylinositol 3-kinase inhibitor, and histone deacetylase inhibitor.
Tomosugi M, Sowa Y*, Yasuda S, Tanaka R, te Riele H, Ikawa H, Koyama M, Sakai T.
Cancer Sci. 2012; 103: 2139-43.
The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells.
Fujiwara J, Sowa Y*, Horinaka M, Koyama M, Wakada M, Miki T, Sakai T.
Int J Oncol. 2012; 40: 1483-91.
Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in human T-cell leukemia Jurkat cells.
Uchiyama H, Sowa Y*, Wakada M, Yogosawa M, Nakanishi R, Horinaka M, Shimazaki C, Taniwaki M, Sakai T.
Cancer Sci. 2010; 101: 728-34.
CDK inhibitor enhances the sensitivity to 5-fluorouracil in colorectal cancer cells.
Takagi K, Sowa Y*, Cevik OM, Nakanishi R, Sakai T.
Int J Oncol. 2008; 32: 1105-10.
The plant alkaloid cryptolepine induces p21WAF1/CIP1 and cell cycle arrest in a human osteosarcoma cell line.
Matsui TA, Sowa Y*, Murata H, Takagi K, Nakanishi R, Aoki S, Yoshikawa M, Kobayashi M, Sakabe T, Kubo T, Sakai T.
Int J Oncol. 2007; 31: 915-22.
Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.
Takagaki N, Sowa Y*, Oki T, Nakanishi R, Yogosawa S, Sakai T.
Int J Oncol. 2005; 26: 185-9.
p53-independent induction of Gadd45 by histone deacetylase inhibitor: coordinate regulation by transcription factors Oct-1 and NF-Y.
Hirose T, Sowa Y*, Takahashi S, Saito S, Yasuda C, Shindo N, Furuichi K, Sakai T.
Oncogene. 2003; 22: 7762-73.
Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor.
Sowa Y*, Orita T, Minamikawa-Hiranabe S, Mizuno T, Nomura H, Sakai T.
Cancer Res. 1999; 59: 4266-70.


*; corresponding author


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e-mail  prevpub@koto.kpu-m.ac.jp



602-8566 Kyoto-shi, Kamigyo-ku Kajii-cho,
Kawaramachi-Hirokoji, JAPAN