Biomedicine & Pharmacotherapy (Nov 2022)
Inhibition of pancreatic cancer-cell growth and metastasis in vivo by a pyrazole compound characterized as a cell-migration inhibitor by an in vitro chemotaxis assay
- Shuichiro Okamoto,
- Kei Miyano,
- Tominari Choshi,
- Norihiko Sugisawa,
- Takashi Nishiyama,
- Rika Kotouge,
- Masahiro Yamamura,
- Masakiyo Sakaguchi,
- Rie Kinoshita,
- Nahoko Tomonobu,
- Naoki Katase,
- Kyo Sasaki,
- Sohji Nishina,
- Keisuke Hino,
- Koji Kurose,
- Mikio Oka,
- Hisako Kubota,
- Tomio Ueno,
- Toshihiro Hirai,
- Hideyo Fujiwara,
- Chikage Kawai,
- Masumi Itadani,
- Aya Morihara,
- Kouji Matsushima,
- Shiro Kanegasaki,
- Robert M. Hoffman,
- Akira Yamauchi,
- Futoshi Kuribayashi
Affiliations
- Shuichiro Okamoto
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Kei Miyano
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Tominari Choshi
- Graduate School of Pharmacy & Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
- Norihiko Sugisawa
- AntiCancer, Inc., San Diego, 92111 CA, USA; Department of Surgery, University of California, San Diego, 92103 CA, USA
- Takashi Nishiyama
- Graduate School of Pharmacy & Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
- Rika Kotouge
- Graduate School of Pharmacy & Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
- Masahiro Yamamura
- Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Masakiyo Sakaguchi
- Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
- Rie Kinoshita
- Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
- Nahoko Tomonobu
- Department of Cell Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
- Naoki Katase
- Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8558, Japan
- Kyo Sasaki
- Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Sohji Nishina
- Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Keisuke Hino
- Department of Gastroenterology and Hepatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; Gastrointestinal Disease Center, Shunan Memorial Hospital, Kudamatsu, Yamaguchi 744-0033, Japan
- Koji Kurose
- Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Mikio Oka
- Department of Immuno-Oncology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Hisako Kubota
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Tomio Ueno
- Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Toshihiro Hirai
- Department of Clinical Nutrition, Kawasaki University of Medical Welfare, Kurashiki, Okayama 701-0193, Japan
- Hideyo Fujiwara
- Department of Pathology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Chikage Kawai
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Masumi Itadani
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Aya Morihara
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Kouji Matsushima
- Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan
- Shiro Kanegasaki
- Department of Lipid Signaling, Research Institute National Center for Global Health and Medicine, Tokyo 162-8655, Japan
- Robert M. Hoffman
- AntiCancer, Inc., San Diego, 92111 CA, USA; Department of Surgery, University of California, San Diego, 92103 CA, USA
- Akira Yamauchi
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; Corresponding author.
- Futoshi Kuribayashi
- Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
- Journal volume & issue
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Vol. 155
p. 113733
Abstract
Pancreatic cancer is recalcitrant to treatment as it is highly metastatic and rapidly progressive. While observing the behavior of human pancreatic BxPC-3 cells using an optical assay device called TAXIScan, we found that several synthetic pyrazole and pyrimidine derivatives inhibited cell migration. One such compound, 14–100, inhibited metastasis of fluorescence-labeled BxPC-3 cells, which were transplanted into the pancreas of nude mice as a subcutaneously grown cancer fragment. Surprisingly, despite its low cytotoxicity, the compound also showed an inhibitory effect on cancer cell proliferation in vivo, suggesting that the compound alters cancer cell characteristics needed to grow in situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound 14–100 could be a good drug candidate against pancreatic cancer.
