GLUT1 inhibition by BAY-876 induces metabolic changes and cell death in human colorectal cancer cells
Masato Hayashi1, Keishi Nakamura2, Shinichi Harada3
1Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan.
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.
Insights
BAY-876, a selective glucose transporter 1 (GLUT1) inhibitor, effectively suppressed colorectal cancer cell proliferation and tumor growth in preclinical models. This GLUT1 inhibitor induced metabolic changes, increased apoptosis, and shows potential for CRC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Glucose transporter 1 (GLUT1) is vital for glucose uptake in tumors.
- GLUT1 inhibitors demonstrate anti-tumor effects by inhibiting cancer cell proliferation.
- BAY-876, a selective GLUT1 inhibitor, has shown efficacy in ovarian and breast cancers.
Purpose of the Study:
- To investigate the anti-proliferative effects of BAY-876 in human colorectal cancer (CRC) cell lines.
- To explore the impact of BAY-876 on cancer cell metabolism and tumor growth.
Main Methods:
- In vitro analysis of BAY-876 effects on HCT116, DLD1, COLO205, LoVo, and Caco-2 cells.
- In vivo assessment using a HCT116-based mouse xenograft model to evaluate tumor-inhibitory effects.
Main Results:
- BAY-876 inhibited proliferation in multiple CRC cell lines (HCT116, DLD1, COLO205, LoVo).
- Observed reduced GLUT1 protein expression, enhanced mitochondrial respiration, increased reactive oxygen species, and elevated apoptosis rates.
- Significant tumor-inhibitory effects and GLUT1 suppression were noted in the xenograft model.
Conclusions:
- BAY-876 treatment induces metabolic alterations and inhibits proliferation in human CRC cells.
- BAY-876 represents a potential novel therapeutic strategy for colorectal cancer treatment.
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