GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells
Abstract Background Glucose transporter 1 (GLUT1) is known to play a crucial role in glucose uptake in malignant tumors. GLUT1 inhibitors reportedly exhibit anti-tumor effects by suppressing cancer cell proliferation. BAY-876, a selective GLUT1 inhibitor, has been shown to inhibit tumor growth in ov...
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BMC
2025-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-14141-9 |
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| author | Masato Hayashi Keishi Nakamura Shinichi Harada Mariko Tanaka Akiko Kobayashi Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Jun Kinoshita Noriyuki Inaki |
| author_facet | Masato Hayashi Keishi Nakamura Shinichi Harada Mariko Tanaka Akiko Kobayashi Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Jun Kinoshita Noriyuki Inaki |
| author_sort | Masato Hayashi |
| collection | DOAJ |
| description | Abstract Background Glucose transporter 1 (GLUT1) is known to play a crucial role in glucose uptake in malignant tumors. GLUT1 inhibitors reportedly exhibit anti-tumor effects by suppressing cancer cell proliferation. BAY-876, a selective GLUT1 inhibitor, has been shown to inhibit tumor growth in ovarian and breast cancers. In this study, we investigated the anti-proliferative effects of BAY-876 treatment in human colorectal cancer (CRC) cell lines. Methods We investigated the metabolic changes and effects on proliferation from BAY-876 treatment in HCT116, DLD1, COLO205, LoVo, and Caco-2 cells in vitro. Additionally, a mouse xenograft model was established using HCT116 cells to examine the tumor-inhibitory effects of BAY-876 treatment in vivo. Results BAY-876 treatment inhibited cell proliferation in HCT116, DLD1, COLO205, and LoVo cells. Reduced GLUT1 protein expression levels were observed through western blot analysis. Flux analysis indicated enhanced mitochondrial respiration, accompanied by increased reactive oxygen species levels and apoptosis rates. Tumor-inhibitory effects were also observed in the xenograft model, with the BAY-876-treated groups showing GLUT1 suppression. Conclusions BAY-876 treatment induced metabolic changes and inhibited cell proliferation in human CRC cell lines. Using BAY-876 is a potential novel approach for treating CRC. |
| format | Article |
| id | doaj-art-88026f4dfdbe4a7dac5c1c0085d9e981 |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-88026f4dfdbe4a7dac5c1c0085d9e9812025-08-20T02:28:08ZengBMCBMC Cancer1471-24072025-04-0125111410.1186/s12885-025-14141-9GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cellsMasato Hayashi0Keishi Nakamura1Shinichi Harada2Mariko Tanaka3Akiko Kobayashi4Hiroto Saito5Toshikatsu Tsuji6Daisuke Yamamoto7Hideki Moriyama8Jun Kinoshita9Noriyuki Inaki10Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Surgery, Public Central Hospital of Matto IshikawaCenter for Biomedical Research and Education, School of Medicine, Kanazawa UniversityCenter for Biomedical Research and Education, School of Medicine, Kanazawa UniversityCenter for Biomedical Research and Education, School of Medicine, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa UniversityAbstract Background Glucose transporter 1 (GLUT1) is known to play a crucial role in glucose uptake in malignant tumors. GLUT1 inhibitors reportedly exhibit anti-tumor effects by suppressing cancer cell proliferation. BAY-876, a selective GLUT1 inhibitor, has been shown to inhibit tumor growth in ovarian and breast cancers. In this study, we investigated the anti-proliferative effects of BAY-876 treatment in human colorectal cancer (CRC) cell lines. Methods We investigated the metabolic changes and effects on proliferation from BAY-876 treatment in HCT116, DLD1, COLO205, LoVo, and Caco-2 cells in vitro. Additionally, a mouse xenograft model was established using HCT116 cells to examine the tumor-inhibitory effects of BAY-876 treatment in vivo. Results BAY-876 treatment inhibited cell proliferation in HCT116, DLD1, COLO205, and LoVo cells. Reduced GLUT1 protein expression levels were observed through western blot analysis. Flux analysis indicated enhanced mitochondrial respiration, accompanied by increased reactive oxygen species levels and apoptosis rates. Tumor-inhibitory effects were also observed in the xenograft model, with the BAY-876-treated groups showing GLUT1 suppression. Conclusions BAY-876 treatment induced metabolic changes and inhibited cell proliferation in human CRC cell lines. Using BAY-876 is a potential novel approach for treating CRC.https://doi.org/10.1186/s12885-025-14141-9Colorectal cancerGlucose transporter 1BAY-876Apoptosis |
| spellingShingle | Masato Hayashi Keishi Nakamura Shinichi Harada Mariko Tanaka Akiko Kobayashi Hiroto Saito Toshikatsu Tsuji Daisuke Yamamoto Hideki Moriyama Jun Kinoshita Noriyuki Inaki GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells BMC Cancer Colorectal cancer Glucose transporter 1 BAY-876 Apoptosis |
| title | GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells |
| title_full | GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells |
| title_fullStr | GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells |
| title_full_unstemmed | GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells |
| title_short | GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells |
| title_sort | glut1 inhibition by bay 876 induces metabolic changes and cell death in human colorectal cancer cells |
| topic | Colorectal cancer Glucose transporter 1 BAY-876 Apoptosis |
| url | https://doi.org/10.1186/s12885-025-14141-9 |
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