Metformin: A Dual-Role Player in Cancer Treatment and Prevention

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 4083 - 4083

Опубликована: Апрель 6, 2024

Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite advancements made in chemotherapy. The emergence of chemoresistance further complicates effectiveness treatment. However, there is growing interest potential metformin, commonly prescribed drug for type 2 diabetes mellitus (T2DM), an adjuvant chemotherapy agent cancer Although precise mechanism action metformin therapy not fully understood, it has been found have pleiotropic effects, including modulation metabolic pathways, reduction inflammation, regulation cellular proliferation. This comprehensive review examines anticancer properties drawing insights from various studies conducted vitro vivo, well clinical trials observational research. discusses mechanisms involving both insulin-dependent independent shedding light on therapeutic different types cancer. Despite promising findings, are challenges that need be addressed, such conflicting outcomes trials, considerations regarding dosing, development resistance. These highlight importance research harness aims this provide contemporary understanding role identify areas future exploration pursuit effective strategies.

Язык: Английский

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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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Metformin enhances anti-cancer properties of resveratrol in MCF-7 breast cancer cells via induction of apoptosis, autophagy and alteration in cell cycle distribution

Biochemical and Biophysical Research Communications, Год журнала: 2022, Номер 644, С. 130 - 139

Опубликована: Дек. 24, 2022

Язык: Английский

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Metformin attenuates symptoms of osteoarthritis: role of genetic diversity of Bcl2 and CXCL16 in OA

Arthritis Research & Therapy, Год журнала: 2023, Номер 25(1)

Опубликована: Март 7, 2023

This study aimed to evaluate the effectiveness of metformin versus placebo in overweight patients with knee osteoarthritis (OA). In addition, assess effects inflammatory mediators and apoptotic proteins pathogenesis OA, genetic polymorphisms two genes, one related apoptosis (rs2279115 Bcl-2) other inflammation (rs2277680 CXCL-16), were investigated.In this double-blind placebo-controlled clinical trial, randomly divided groups, group receiving (n = 44) an identical inert for 4 consecutive months (starting dose 0.5 g/day first week, increase 1 second further 1.5 remaining period). Another healthy individuals 92) no history diagnosis OA included order role genetics OA. The outcome treatment regimen was evaluated using Knee Injury Osteoarthritis Outcome Score (KOOS) questionnaire. frequency variants rs2277680 (A181V) rs2279115 (938C>A) determined extracted DNAs PCR-RFLP method.Our results indicated scores pain (P ≤ 0.0001), activity daily living (ADL) sport recreation (Sport/Rec) quality life (QOL) 0.003) total KOOS questionnaire compared group. Susceptibility associated age, gender, family history, CC genotype 938C>A (Pa 0.001; OR 5.2; 95% CI 2.0-13.7), GG+GA genotypes A181V 0.04; 2.1; 1.1-10.5). C allele 2.2; 1.1-9.8) G 0.02; 1.1-4.8) also OA.Our findings support possible beneficial on improving pain, ADL, Sport/Rec, QOL patients. Our association between Bcl-2 CXCL-16

Язык: Английский

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

Опубликована: Март 22, 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 of survival outcomes prognosis. The synergistic effects 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 metformin's 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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Anexelekto (AXL) no more: microRNA-155 (miR-155) controls the “Uncontrolled” in SARS-CoV-2

Human Cell, Год журнала: 2024, Номер 37(3), С. 582 - 592

Опубликована: Март 12, 2024

Язык: Английский

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MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets

Frontiers in Molecular Biosciences, Год журнала: 2021, Номер 8

Опубликована: Окт. 26, 2021

The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and significantly the development angiogenesis process different types cancer, including BC. There’s increasing evidence showed various miRNAs play a significant disease processes; specifically, they observed over-expressed wide range diseases process. However, more studies required reach best findings identify link among miRNA expression, angiogenic pathways, immune response-related genes find new therapeutic targets. Here, we summarized recent updates on signatures their cellular targets angiogenetic discussed strategies associated with miRNA-based as anti-angiogenic response.

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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Circular RNA circ‐TNRC6B inhibits the proliferation and invasion of esophageal squamous cell carcinoma cells by regulating the miR‐452‐5p/DAG1 axis

Molecular Oncology, Год журнала: 2023, Номер 17(7), С. 1437 - 1452

Опубликована: Апрель 4, 2023

Previous studies have uncovered the key role of circular RNAs (circRNAs) in various diseases, including cancer. However, growth‐inhibitory effects circRNAs on esophageal squamous cell carcinoma (ESCC) not been completely elucidated. This study characterized a newly identified circRNA derived from exons 9–13 TNRC6B (named circ‐TNRC6B). The expression circ‐TNRC6B ESCC tissues was markedly downregulated when compared to that non‐tumor tissues. In 53 cases, negatively correlated with T stage. Multivariate Cox regression analysis showed upregulation an independent protective factor for patients' prognosis. Overexpression and knockdown functional experiments demonstrated inhibited proliferation, migration, invasion. RNA immunoprecipitation dual‐luciferase reporter assays sponges oncogenic miR‐452‐5p upregulate activity DAG1. Treatment inhibitor partially reversed circ‐TNRC6B‐induced changes biological behavior cells. These findings exerts tumor‐suppressing effect through miR‐452‐5p/DAG1 axis. Thus, is potential prognostic biomarker clinical management ESCC.

Язык: Английский

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Metformin Exhibits Anti‐Inflammatory Effects by Regulating microRNA‐451/CXCL16 and B Cell Leukemia/Lymphoma 2 in Patients With Osteoarthritis

ACR Open Rheumatology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Objective Osteoarthritis (OA) is the most common cause of chronic disability in joints among older individuals. The primary goal OA treatment pain relief to improve quality life. Inflammation and aging are involved pathogenesis OA. In this study, we evaluated ability metformin regulate microRNAs, such as miR‐451 miR‐15b, their target proteins, CXCL16 B cell leukemia/lymphoma 2 (BCL‐2), inflammation apoptosis. Methods double‐blind placebo‐controlled clinical trial, patients were randomly divided into two groups: one receiving other a placebo for four months (starting at 0.5 g/day first week, increasing 1 second 1.5 remaining period). addition evaluating response using Knee Injury Outcome Score questionnaire, miR‐15b expression levels detected real‐time polymerase chain reaction. serum BCL‐2 enzyme‐linked immunosorbent assay kits before (time zero) after (month four). Results Metformin increased simultaneously with reduction, whereas did not change significantly treatment. Also, decreased Conclusion effects reducing can be attributed many factors, including its anti‐inflammatory antiaging effects. Our findings suggest that may reduce through regulation miR‐451/CXCL16 BCL‐2.

Язык: Английский

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