Metformin in Cervical Cancer: Metabolic Reprogramming
Abstract
The reprogrammed metabolism plays a crucial role in intensively proliferating tumor cells to meet high energetic demands and adapt to metastasis and invasion. Metformin may counteract flexible metabolic phenotype of cervical cancer cells by restraining aerobic glycolysis (Warburg effect) and promoting mitochondrial-based metabolism. Metformin inhibits master oncogene c-Myc as well as hypoxia-inducible factor 1 (HIF-1α) and suppresses its downstream glycolytic regulatory enzymes and glucose transporters. Metformin targets bioenergetics of cervical cancer cells with aggressive phenotype and regulates the expression of enzymes controlling tricarboxylic acid cycle (TCA cycle) supplementation with substrates, glucose, and glutamine. The exposition of cervical tumor cells to Metformin alleviates their migratory capacity, restrains epithelial-to-mesenchymal transition (EMT) program implementation, and elucidates oxidative stress, which results in massive cell death due to apoptosis. The metabolic alterations caused by Metformin are specific to cancer cells. In summary, Metformin exerts antitumor effect in cervical cancer cells by regulating specific molecular targets in reprogrammed metabolism. Metformin selectively modulates metabolic pathways and thus may be potentially used in new precisely targeted therapeutic strategies for cervical cancer.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.