1. Metformin Radiosensitizing Effect on Hypoxic Oral Squamous Cell Carcinoma Cells by GAPDH and TAGLN2.
- Author
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Santos EM, Farias LC, Guimarães TA, Santos EMS, de Jesus SF, de Souza MG, de Souza PC, Santiago L, D'Angelo MFSV, De-Paula AMB, Santos SHS, and Guimarães ALS
- Subjects
- Humans, Cell Line, Tumor, Cell Movement drug effects, Radiation Tolerance drug effects, Reactive Oxygen Species metabolism, Proteomics, Glyceraldehyde-3-Phosphate Dehydrogenases, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), Cell Hypoxia drug effects, Tumor Hypoxia drug effects, Metformin pharmacology, Metformin therapeutic use, Mouth Neoplasms radiotherapy, Radiation-Sensitizing Agents pharmacology, Carcinoma, Squamous Cell
- Abstract
Objective: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells., Methods: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies., Results: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53., Conclusions: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2024
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