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Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo.
Kubokura, Naoya; Takahashi-Yanaga, Fumi; Arioka, Masaki; Yoshihara, Tatsuya; Igawa, Kazunobu; Tomooka, Katsuhiko; Morimoto, Sachio; Nakatsu, Yoshimichi; Tsuzuki, Teruhisa; Nakabeppu, Yusaku; Matsumoto, Takayuki; Kitazono, Takanari; Sasaguri, Toshiyuki.
Afiliación
  • Kubokura N; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Department of Medicine and Clinical Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Takahashi-Yanaga F; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Global Medical Science Education Unit, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. Electronic address: yanaga@clipharm.med.kyushu-u.ac.jp.
  • Arioka M; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Yoshihara T; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Igawa K; Department of Molecular and Material Science, Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, 816-8580, Japan.
  • Tomooka K; Department of Molecular and Material Science, Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, 816-8580, Japan.
  • Morimoto S; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Nakatsu Y; Department of Medical Biophysics and Radiation Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Tsuzuki T; Department of Medical Biophysics and Radiation Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
  • Nakabeppu Y; Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
  • Matsumoto T; Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, 020-0023, Japan.
  • Kitazono T; Department of Medicine and Clinical Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Sasaguri T; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
J Pharmacol Sci ; 127(4): 446-55, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25913757
Differentiation-inducing factor-1 (DIF-1) produced by Dictyostelium discoideum strongly inhibits the proliferation of various types of cancer cells by suppression of the Wnt/ß-catenin signal transduction pathway. In the present study, we examined the effect of differentiation-inducing factor-3 (DIF-3), a monochlorinated metabolite of DIF-1 that is also produced by D. discoideum, on human colon cancer cell lines HCT-116 and DLD-1. DIF-3 strongly inhibited cell proliferation by arresting the cell cycle at the G0/G1 phase. DIF-3 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via activation of GSK-3ß in a time and dose-dependent manner. In addition, DIF-3 suppressed the expression of T-cell factor 7-like 2, a key transcription factor in the Wnt/ß-catenin signaling pathway, thereby reducing the mRNA levels of cyclin D1 and c-Myc. Subsequently, we examined the in vivo effects of DIF-3 in Mutyh(-/-) mice with oxidative stress-induced intestinal cancers. Repeated oral administration of DIF-3 markedly reduced the number and size of cancers at a level comparable to that of DIF-1. These data suggest that DIF-3 inhibits intestinal cancer cell proliferation in vitro and in vivo, probably by mechanisms similar to those identified in DIF-1 actions, and that DIF-3 may be a potential novel anti-cancer agent.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Colon / Proliferación Celular / Hexanonas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Colon / Proliferación Celular / Hexanonas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Pharmacol Sci Asunto de la revista: FARMACOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón