Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo
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/β-catenin signal transduction pathway. In the present study, we examined the effect of differentiation-inducing factor-3 (DIF-...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-04-01
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| Series: | Journal of Pharmacological Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315000614 |
| _version_ | 1811241903820111872 |
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| author | Naoya Kubokura Fumi Takahashi-Yanaga Masaki Arioka Tatsuya Yoshihara Kazunobu Igawa Katsuhiko Tomooka Sachio Morimoto Yoshimichi Nakatsu Teruhisa Tsuzuki Yusaku Nakabeppu Takayuki Matsumoto Takanari Kitazono Toshiyuki Sasaguri |
| author_facet | Naoya Kubokura Fumi Takahashi-Yanaga Masaki Arioka Tatsuya Yoshihara Kazunobu Igawa Katsuhiko Tomooka Sachio Morimoto Yoshimichi Nakatsu Teruhisa Tsuzuki Yusaku Nakabeppu Takayuki Matsumoto Takanari Kitazono Toshiyuki Sasaguri |
| author_sort | Naoya Kubokura |
| collection | DOAJ |
| description | 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/β-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-3β 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/β-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. |
| first_indexed | 2024-04-12T13:43:12Z |
| format | Article |
| id | doaj.art-a01a3be87fcb40d49109f332c358a672 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T13:43:12Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-a01a3be87fcb40d49109f332c358a6722022-12-22T03:30:47ZengElsevierJournal of Pharmacological Sciences1347-86132015-04-01127444645510.1016/j.jphs.2015.03.005Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivoNaoya Kubokura0Fumi Takahashi-Yanaga1Masaki Arioka2Tatsuya Yoshihara3Kazunobu Igawa4Katsuhiko Tomooka5Sachio Morimoto6Yoshimichi Nakatsu7Teruhisa Tsuzuki8Yusaku Nakabeppu9Takayuki Matsumoto10Takanari Kitazono11Toshiyuki Sasaguri12Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Molecular and Material Science, Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, 816-8580, JapanDepartment of Molecular and Material Science, Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga, 816-8580, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Medical Biophysics and Radiation Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDepartment of Medical Biophysics and Radiation Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDivision of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, JapanDivision of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, 020-0023, JapanDepartment of Medicine and Clinical Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, JapanDifferentiation-inducing factor-1 (DIF-1) produced by Dictyostelium discoideum strongly inhibits the proliferation of various types of cancer cells by suppression of the Wnt/β-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-3β 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/β-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.http://www.sciencedirect.com/science/article/pii/S1347861315000614c-Myccyclin D1DIF-3TCF7L2Wnt/β-catenin signaling pathway |
| spellingShingle | Naoya Kubokura Fumi Takahashi-Yanaga Masaki Arioka Tatsuya Yoshihara Kazunobu Igawa Katsuhiko Tomooka Sachio Morimoto Yoshimichi Nakatsu Teruhisa Tsuzuki Yusaku Nakabeppu Takayuki Matsumoto Takanari Kitazono Toshiyuki Sasaguri Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo Journal of Pharmacological Sciences c-Myc cyclin D1 DIF-3 TCF7L2 Wnt/β-catenin signaling pathway |
| title | Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo |
| title_full | Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo |
| title_fullStr | Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo |
| title_full_unstemmed | Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo |
| title_short | Differentiation-inducing factor-3 inhibits intestinal tumor growth in vitro and in vivo |
| title_sort | differentiation inducing factor 3 inhibits intestinal tumor growth in vitro and in vivo |
| topic | c-Myc cyclin D1 DIF-3 TCF7L2 Wnt/β-catenin signaling pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1347861315000614 |
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