GLUT1 as a Potential Therapeutic Target in Glioblastoma
Abstract
:1. Introduction
1.1. The Role of GLUT1 in Glucose Transport, Cancer Metabolism, and Tumor Progression
1.2. Hypoxia and the Expression of GLUT1 in Cancer Cells
1.3. The Role of GLUT1 in Glioblastoma
1.4. GLUT1 as a Therapeutic Target in Glioblastoma
1.5. Clinical and Prognostic Implications of GLUT1 in GBM Therapy
2. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study, Year | Type of Study | Cell Line | Animal Model | Drug | Mechanism of Action | Dose | Results |
---|---|---|---|---|---|---|---|
Guda et al., 2019 [16] | In vitro | GSC33 and GSC28 | N/A | Fasentin | TUBB4 inhibitor | Fasentin at 25 µM and 50 µM dose | Decreased sphere formation over 15 days of treatment |
Azzalin et al., 2017 [54] | In vitro and In vivo |
U87MG, Hu197 (stable human GBM cell line) and GBM-P1 (primary human GBM cell culture) And GL261 (mouse GBM cell line) | C57BlC inoculated with GL261 GBM cells orthotopic GBM mouse model |
Indinavir (IDV) and Ritonavir (RTV) in combination with TMZ and BCNU | Inhibition of GLUT1/SLC2A transporter | 45 µM and 55 µM of RTV in vitro and BCNU alone (2.5 mg/kg), a combination of RTV (100 mg/kg) and BCNU (1.5 mg/kg), or a combination of RTV (100 mg/kg) and BCNU (2.5 mg/kg) in vivo | Median survival was approximately 18 days for the BCNU-only group and about 37 days for the BCNU 1 + RTV group. RTV but not IDV decreased glycolytic activity and cell growth in vitro. Mice treated with RTV + BCNU have improved survival than BCNU alone, also enhanced |
Atif et al., 2019 [55] | In vivo | U118MG (Human GBM cell line), U87dEGFR (modified human cell line) and U87MG-luc | Adult male athymic nude mice inoculated with U87MG-luc orthotopic GBM mouse model | Progesterone | Inhibition of GLUT1, GAPDH and cytoplasmic FoxO1 activity | 10–80 µM in vitro and low dose (8 mg/kg) and high dose (100 mg/kg) in vivo | Progesterone treatment significantly enhanced the survival of tumor-bearing mice by 43% compared to vehicle-treated mice without toxicity |
Tianliang et al., 2024 [56] | In vitro and In vivo | Mouse GBM cells of GL261, Human GBM cell lines of U87 and U251, Mouse macrophage cell lines of RAW264.7 | C57BL/6J mice subcutaneously injected with GL261 cells And C57BL/6J mice inoculated with GL261 or GL261-luc orthotopic GBM mouse model | BAY-876 and PD-1/PD-l1 blocker BMS-1 | Inhibitor of GLUT1 | 1, 2, 4 ng mL−1 of BAY-876 in vitro and 2 nm of BAY-876 in vivo | The median survival of tumor-bearing mice treated with BAY-876 increased to 36.5 days compared to 28.5 days in the control group. Treatment with BMS-1 further prolonged survival to 45 days (endpoint) |
Shibuya et al., 2015 [57] | In vitro and In vivo | GS-Y03 GBM stem cell and other cancer stem cells (PANC-1 CSLC, and A2780) | male BALB/cAJcl-nu/nu mice subcutaneously implanted with GS-Y03 cell line and other cancer stem cells | WZB117 | GLUT1 inhibitor | WZB117 4 mg/mL in DMSO was diluted in PBS to prepare 200 μL for each injection in vivo | In vivo, the tumor size between control and WZB117-treated tumor-bearing mice was statistically significant, with the treated group having a smaller tumor volume. |
Landis et al., 2018 [58] | In vitro | GBM (PDX) D456, 1016, JX12, and JX14 | N/A | SRI-37683 and SRI-37684 | GLUT 1 inhibitor | 50 µM SRI-37683 and SRI-37684 | There was a 40–50% inhibition of glucose uptake in all tested cell lines |
Leone S. et al., 2008 [59] | In vitro | U-87MG | N/A | Resveratrol | GLUT1, STAT3 inhibitor | 20 µM of resveratrol and 5 Gy; 180 KV X-rays | 20 µM of resveratrol and 5 Gy; 180 KV X-rays |
Yand YP et al., 2012 [60] | In vitro and In vivo | CD133 and CD133+ cells from a patient | SCID mice (BALB/c strain) orthotopic GBM mouse model | Resveratrol | GLUT1, STAT3 inhibitor | RV 100 µM 2, 4, 6, 8 and 10 Gy | Suppression of STAT3 and induction of apoptosis of tumor cells. Treatment group median survival was 10 weeks vs. 4 weeks in the control group |
Wang L et al., 2015 [61] | In vitro and in vivo | Human Glioma SU-2 patient derived | male nude (BALB/c) mice | Resveratrol | GLUT1, STAT3 inhibitor | RV 75 µmol/L (for in vitro) and 150 mg/kg/day (for in vivo) ip, and 2, 4 and 6 Gy; 6 MV X-rays | Increased radiosensitivity of cells, prevention of renewal and stemness, increased apoptosis, inhibition of DNA repair. Decreased relative tumor volume in nude mice in treated group |
Khoei S et al., 2016 [62] | In vitro | U87MG GBM cell line | N/A | Resveratrol | GLUT1, STAT3 inhibitor | RV 20 µM and 2 Gy; 1.25 MeV | Decreased colony number, increased DNA damage and increased radiosensitivity |
Ozturk Y et al., 2019 [63] | In vitro | DBTRG GBM cell line | N/A | Resveratrol | GLUT1, STAT3 inhibitor | RV 50 µM and 50 µM of paclitaxal | Increased mitochondrial ROS levels and activation of TRMP2 channel, increased caspase activity and Ca+ influx through TRMP2 channel |
Huang H. et al., 2012 [64] | In vitro | T98G GBM cell line | N/A | Resveratrol | GLUT1, STAT3 inhibitor | RV 100 µM and TMZ 100 µM | Increased chemosensitivity, increased apoptosis, decreased intracellular translocation of NF-kB, and repression of MGMT expression |
Li H et al., 2016 [65] | In vitro and in vivo | GBM initiating cells (GICs) from 2 patients | female NOD/SCID mice inoculated by GICs | Resveratrol | GLUT1, STAT3 inhibitor | RV 20 and 40 µM and TMZ; 200 and 400 µM (for in vitro); RV 12.5 mg/kg/day ip and TMZ 68 mg/kg/day (in vivo); oral | Induction of apoptosis and activation of p53/pATR/pATM/DSBs pathways, inhibition of self renewal and decreased cell stemness, inactivation of STAT3 and decreased tumor volume |
Yang HC et al., 2019 [66] | In vitro and in vivo | U251, T98G, U138, A172, LN229, and normal human astrocytes | N/A | Resveratrol | GLUT1, STAT3 inhibitor | RV 2, 4, 8, 10, 16 and 32 µM and TMZ; 400 µM (in vitro); RV 10 mg/kg/day; ip and TMZ 25 mg/kg//day (in vivo); ip | Decreased cell viability and proliferation, increased apoptosis, supression of Wnt pathway and repression of MGMT expression |
Liu Y et al., 2020 [67] | In vitro | RG-2, LN-18, LN-428 | NA | Resveratrol | GLUT1, STAT3 inhibitor | RV 25, 50, 75 and 100 µM and TMZ 250, 500, 750 and 1000 µM | Inhibition of cells growth repression of MGMT expression, decreased STAT3 decreased Bcl2 |
Yuan Y et al., 2012 [68] | In vitro and in vivo | SHG44 GBM cell line | Female BALB/cA nude mice inoculated with SHG44 orthotropic glioma model | Resveratrol | GLUT1, STAT3 inhibitor | RV 10 µM and TMZ 100 µM (in vitro); RV 40 mg/kg/day ip and TMZ 68 mg/kg/day (in vivo) oral | Cell cycle arrest, downregulation of MMP9 expression, inhibition of cell migration, increased mitochondrial ROS, downregulation og Bcl2, inhibition of mTOR and increased expression of GFAP. Decreased tumor volume |
Lin CJ et al., 2012 [69] | In vitro and in vivo | U87 MG and GBM8401 GBM cell lines | female nude mice BALB/c nu/nu subcutaneously injected with U87MG cells | Resveratrol | GLUT1, STAT3 inhibitor | RV 10 µM and TMZ; 100–400 µM (in vitro); RV 12.5 mg/kg/day ip and TMZ 10 mg/kg/day (in vivo) ip | Increased cell death, increased apoptosis, chemosensitivity. Decreased tumor volume. Decreased ERK activity and LC3-II protein levels and increased cleavage of PARP |
Trial ID | Year | Cancer Type | Resveretrol Dose | Phase | Country | Results |
---|---|---|---|---|---|---|
NCT01476592 | 2011 | Low grade gastrointestinal tumors | 2.5 g/2 times a day for three cycles, oral | Not applicable | USA | Study completed in 2017 but results are unavailable |
NCT00920803 [75] | 2008 | Colorectal cancer and hepatic metastasis | SRT501 5.0 g daily for 14 days, oral | Phase 1 | UK | Hepatic tissue was found to contain resveratrol |
NCT00256334 [76] | 2005 | Colon cancer | Four dose cohorts—plant derived resveratrol tablets 80 mg/day or 20 mg/day or Freeze dried grape powder (GP) (containing reveretrol) at 120 mg/day or 80 mg/day, oral | Phase 1 | USA | GP was successful in tarteting and inhibiting Wnt target gene, |
NCT00920556 [77] | 2009 | Multiple Myeloma | SRT501 5 g/day for 20 days in a 21 day cycle for upto 12 cycles, oral | Phase 2 | UK | Unacceptable safety profile with minimal efficacy in recurrent multiple myeloma. |
NCT00433576 [78] | 2006 | Colorectal cancer | Oral resveretrol for 9 days | Phase 1 | USA | Study completed in 2009 but results are unavailable. The objective of the study was to determine oral dose and colon mucosal levels and correlate levels of COX-2 and M1G in colorectal cancer tissue and WBCs |
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Ruchika, F.; Suvarnapathaki, S.; Serrano-Farias, A.; Bettegowda, C.; Rincon-Torroella, J. GLUT1 as a Potential Therapeutic Target in Glioblastoma. Brain Sci. 2025, 15, 585. https://doi.org/10.3390/brainsci15060585
Ruchika F, Suvarnapathaki S, Serrano-Farias A, Bettegowda C, Rincon-Torroella J. GLUT1 as a Potential Therapeutic Target in Glioblastoma. Brain Sciences. 2025; 15(6):585. https://doi.org/10.3390/brainsci15060585
Chicago/Turabian StyleRuchika, FNU, Sanika Suvarnapathaki, Antolin Serrano-Farias, Chetan Bettegowda, and Jordina Rincon-Torroella. 2025. "GLUT1 as a Potential Therapeutic Target in Glioblastoma" Brain Sciences 15, no. 6: 585. https://doi.org/10.3390/brainsci15060585
APA StyleRuchika, F., Suvarnapathaki, S., Serrano-Farias, A., Bettegowda, C., & Rincon-Torroella, J. (2025). GLUT1 as a Potential Therapeutic Target in Glioblastoma. Brain Sciences, 15(6), 585. https://doi.org/10.3390/brainsci15060585