Metformin: From Diabetes to Cancer—Unveiling Molecular Mechanisms and Therapeutic Strategies

Biology, Год журнала: 2024, Номер 13(5), С. 302 - 302

Опубликована: Апрель 27, 2024

Metformin, a widely used anti-diabetic drug, has garnered attention for its potential in cancer management, particularly breast and colorectal cancer. It is established that metformin reduces mitochondrial respiration, but specific molecular targets within mitochondria vary. Proposed mechanisms include inhibiting respiratory chain Complex I and/or IV, glycerophosphate dehydrogenase, among others. These actions lead to cellular energy deficits, redox state changes, several changes reduce hyperglycemia type 2 diabetic patients. Clinical evidence supports metformin’s role prevention diabetes mellitus Moreover, these patients with cancer, consumption leads an improvement survival outcomes prognosis. The synergistic effects of chemotherapy immunotherapy highlights as adjunctive therapy However, nuanced findings underscore the need further research stratification by subtype, This comprehensive review integrates metformin-related from epidemiological, clinical, preclinical studies Here, we discuss current addressed define bioavailability efficacy, exploring novel metformin-based compounds drug delivery systems, including derivatives targeting mitochondria, combination therapies, nanoformulations, showing enhanced anticancer effects.

Язык: Английский

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A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer

Cancers, Год журнала: 2024, Номер 16(17), С. 3017 - 3017

Опубликована: Авг. 29, 2024

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, specific microbiota, contribute to the disease’s prevalence. Recently, compelling association between diabetes mellitus (DM) cancer has been identified, with metformin, widely used antidiabetic drug, emerging as potential therapeutic agent across various cancers, OSCC. This review explores both preclinical clinical studies understand mechanisms by which metformin may exert anticancer effects, such inhibiting proliferation, inducing apoptosis, enhancing efficacy existing treatments. Preclinical demonstrate that modulates crucial metabolic pathways, reduces inflammation, impacts cellular thereby potentially lowering improving patient outcomes. Additionally, metformin’s ability reverse epithelial-to-mesenchymal transition (EMT), regulate LIN28/let-7 axis, role in head neck (HNSCC) are examined through experimental models. In contexts, shows promise outcomes reducing recurrence rates, although challenges drug interactions, complex dosing regimens, risks vitamin B12 deficiency remain. Future research should focus on optimizing application, investigating synergistic effects other therapies, conducting rigorous trials validate OSCC treatment. dual exploration underscores play transformative management care, revolutionizing strategies.

Язык: Английский

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Hesperetin-Enhanced Metformin to Alleviate Cognitive Impairment via Gut–Brain Axis in Type 2 Diabetes Rats

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(5), С. 1923 - 1923

Опубликована: Фев. 23, 2025

Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and decline. The use of metformin treating impairment remains controversial. present study found that hesperetin, flavanone derived from citrus peel, enhanced metformin's efficacy in reducing blood sugar levels, improving sensitivity, ameliorating diabetic rats. Additionally, it reduced required dosage to one-third its conventional dose. Transcriptome analysis 16S rRNA sequencing revealed activation cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic (BDNF) pathways benefited regulation gut microbiota promotion short-chain fatty acid (SCFA) producers such Romboutsia. Furthermore, this demonstrated hesperetin supplementation counteracted upregulation β-site amyloid precursor cleaving enzyme 1 (BACE1), pathological Alzheimer's disease (AD) was induced by metformin. Our findings reveal can be used supplementary treatment associated with diabetes.

Язык: Английский

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Rhizoma Atractylodis Macrocephalae reduces HFD-induced NAFLD in mice through activated AMPK mediated inhibition of fatty acid synthesis

Liver Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

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Dual‐Responsive Immunomodulatory RNAi Nanoplatform for Effective Immune Checkpoint Blockade and Enhanced Cancer Immunotherapy

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 20, 2025

Abstract Immune checkpoint blockade (ICB) therapy has become the first‐line treatment for cancer patients. However, low response rate remains a clinical pain‐point. Anti‐hyperglycemic drug metformin shown remarkable anticancer effect with unique characteristic of modulating tumor immune microenvironment (TIME). Therefore, combining ICB could be promising strategy enhanced immunotherapy, which however challenged due to bioavailability and severe adverse effects metformin. This work herein designs an amphiphilic reduction‐responsive prodrug, complex small interfering RNA (siRNA) then co‐assemble endosomal pH‐responsive PEGylated polymer form dual‐responsive immunomodulatory RNAi nanoplatform. Using orthotopic metastatic breast (BCa) models, this demonstrates that nanoplatform silence PD‐L1 expression on BCa cells suppress their proliferation via activating AMP‐activated protein kinase (AMPK). Moreover, AMPK activation secretion tumor‐derived transforming growth factor β (TGF‐β) interleukin 6 (IL‐6), enhance maturation dendritic (DCs) CD8 + T impair infiltration regulatory (Tregs), myeloid‐derived suppressor (MDSCs), tumor‐associated macrophages (TAMs), ultimately achieving goal immunotherapy significant inhibition growth.

Язык: Английский

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Metformin in Antiviral Therapy: Evidence and Perspectives

Viruses, Год журнала: 2024, Номер 16(12), С. 1938 - 1938

Опубликована: Дек. 18, 2024

Metformin, a widely used antidiabetic medication, has emerged as promising broad-spectrum antiviral agent due to its ability modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes energy reserves that viruses rely on, effectively limiting the replication of pathogens such influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting mTOR pathway, crucial protein synthesis reactivation, is particularly significant managing infections caused by CMV, EBV. Furthermore, reduces oxidative stress reactive oxygen species (ROS), which are critical replicating arboviruses Zika dengue. The drug also regulates immune responses, differentiation, inflammation, disrupting life cycle HPV potentially other viruses. These diverse mechanisms suppress replication, enhance system functionality, contribute better clinical outcomes. This multifaceted approach highlights metformin’s potential an adjunctive therapy treating wide range infections.

Язык: Английский

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Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Дек. 11, 2023

Cancer represents the main cause of death worldwide. Thyroid cancer (TC) shows an overall good rate survival, however there is a percentage patients that do not respond or are refractory to common therapies. Thus new therapeutics strategies required. In past decade, drug repositioning become very important in field therapy. This approach several advantages including saving of: i) time, ii) costs, iii) de novo studies regarding safety (just characterized) drug. Regarding TC, few considered potential drugs. On other hand, certain anti-diabetic drugs, were focus interesting on TC therapy, view fact they exhibited anti-tumor effects. Among these compounds, all judjed as appropriate for repositioning, well documented side However, just give examples biguanides, DPP-4-inhibitors and Thiazolidinediones found exert strong anti-cancer effects TC. Indeed, their spaced from induction citotoxicity inhibition metastatic spread, de-differentiation cells modulation microenvironment. Thus, multifacial effect compounds would make basis also combinatory strategies. The present review aimed at discuss data drugs recently showed repositioning. Specific repositionable treatment will be provided.

Язык: Английский

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Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 27, 2024

Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on potential EVs derived from human periodontal ligament cells (PDLSCs) for periodontitis. PDLSCs were cultured in medium with or without metformin, supernatant was then collected separately to extract metformin-treated (M-EVs). After identifying characteristics, we evaluated M-EVs vivo vitro. Osteogenic differentiation markedly enhanced after treatment, effect dramatically inhibited GW4896, an inhibitor EVs' secretion. significantly increased yields improved their cell proliferation, migration, differentiation. Moreover, ability inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption reduced groups when compared periodontitis group, while group showed lowest levels loss. promoted partly through pathway secretion PDLSCs-EVs superior pro-osteogenic potential, thus improving

Язык: Английский

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Sulfenamide formation – chemical and biochemical reactions and their applications in cell biology

Journal of Sulfur Chemistry, Год журнала: 2023, Номер 45(2), С. 293 - 312

Опубликована: Ноя. 1, 2023

Sulfenamides are organosulfur compounds that contain a single bond between nitrogen and sulfur in their structures. Sulfur can react with nucleophiles to yield new compounds. The having nitrogen–sulfur bonds used polymers for variety of purposes, including medicines, agrochemicals, veterinary medications, environmental studies. This review will examine several chemical reactions lead sulfenamide production as well how they cell biology biochemical applications.

Язык: Английский

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