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Journal of Translational Medicine Feb 2023Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs... (Review)
Review
Breast cancer (BC) is the second most common cancer and cause of death in women. In recent years many studies investigated the association of long non-coding RNAs (lncRNAs), as novel genetic factors, on BC risk, survival, clinical and pathological features. Recent studies also investigated the roles of metformin treatment as the firstline treatment for type 2 diabetes (T2D) played in lncRNAs expression/regulation or BC incidence, outcome, mortality and survival, separately. This comprehensive study aimed to review lncRNAs associated with BC features and identify metformin-regulated lncRNAs and their mechanisms of action on BC or other types of cancers. Finally, metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, by several molecular mechanisms have been described in this review. In addition, metformin action on other types of cancers by regulating ten lncRNAs including AC006160.1, Loc100506691, lncRNA-AF085935, SNHG7, HULC, UCA1, H19, MALAT1, AFAP1-AS1, AC026904.1 is described.
Topics: Female; Humans; Breast Neoplasms; RNA, Long Noncoding; Metformin; Diabetes Mellitus, Type 2
PubMed: 36849958
DOI: 10.1186/s12967-023-03909-x -
Journal of Diabetes Investigation Jul 2018Recent evidence suggests that metformin exerts glucose-lowering effects via its action in the gut. The accumulation in the colon of F-labeled fluorodeoxyglucose (FDG),...
Recent evidence suggests that metformin exerts glucose-lowering effects via its action in the gut. The accumulation in the colon of F-labeled fluorodeoxyglucose (FDG), a nonmetabolizable derivative of glucose, is markedly augmented after metformin administration, indicating that metformin affects the handling of glucose in colon whereas the underlying mechanism and the significance to glucose metabolism of the finding remain to be determined.
Topics: Animals; Gastrointestinal Absorption; Gastrointestinal Microbiome; Gastrointestinal Tract; Glucose; Humans; Hypoglycemic Agents; Metformin
PubMed: 29777629
DOI: 10.1111/jdi.12864 -
International Journal of Molecular... Dec 2022Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other... (Review)
Review
Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.
Topics: Humans; Biocompatible Materials; Tissue Engineering; Metformin; Osteogenesis; AMP-Activated Protein Kinases; Diabetes Mellitus, Type 2; Tissue Scaffolds; Cell Differentiation; Bone Regeneration
PubMed: 36555544
DOI: 10.3390/ijms232415905 -
Biomedicine & Pharmacotherapy =... Dec 2022Metformin as a first-line drug for type 2 diabetes mellitus(T2DM) treatment is widely studied. Metformin can reduce liver glucose output and improve insulin resistance.... (Review)
Review
Metformin as a first-line drug for type 2 diabetes mellitus(T2DM) treatment is widely studied. Metformin can reduce liver glucose output and improve insulin resistance. Recent evidence from in vivo and in vitro has confirmed that metformin can transport across the blood-brain barrier(BBB) and activate specific neurons and neuroglia to exert neurological actions, however, the specific effect of metformin regulation on CNS is still obscure. In this review, we summarized current evidence from preclinical evidence focusing on the regulatory role of metformin in CNS and found that metformin can exert potential neuroprotective, neurotrophic, and neurogenesis-stimulated actions; besides, metformin also exerts antiinflammatory effect by inhibiting microglial activates and regulating microglial polarization. These findings indicate there might be extensive pharmacological efficacy and therapeutic insights of metformin in neurological diseases' clinical application.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Central Nervous System; Insulin Resistance; Microglia; Hypoglycemic Agents; AMP-Activated Protein Kinases
PubMed: 36244266
DOI: 10.1016/j.biopha.2022.113686 -
Diabetologia Sep 2017Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has... (Review)
Review
Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has been confined to observational studies. In early years, perceived safety concerns and lack of availability of the drug in many countries acted as a barrier to use. More recently, RCTs have begun to examine the role of metformin in pregnancy in much-needed detail. However, this evidence base has been interpreted differently in different countries, leading to very wide variation in its current application in pregnancy. In this short review, we will discuss the history of metformin in pregnancy and highlight some of the key clinical trials. We will then consider some of the remaining controversies associated with metformin use in pregnancy, most important of these being the potential for long-term 'programming' effects on the fetus as a result of metformin being able to cross the placenta. We will also consider clinical situations where metformin might be avoided. Finally, we will discuss some future directions for this drug as it reaches its sixtieth anniversary.
Topics: Female; Humans; Hypoglycemic Agents; Metformin; Pregnancy; Teratogenesis
PubMed: 28770325
DOI: 10.1007/s00125-017-4351-y -
Ginekologia Polska 2022The results of preclinical, epidemiological and clinical studies have shown that metformin, the main drug used in the treatment of type 2 diabetes, has antitumor...
The results of preclinical, epidemiological and clinical studies have shown that metformin, the main drug used in the treatment of type 2 diabetes, has antitumor activity. Metformin reduces the incidence of malignant neoplasms in various locations, including gynaecological tumours. It lowers morbidity, has a positive effect on the course of the disease and reduces mortality. The mechanism of the antitumor action of metformin is pleiotropic and involves several signalling pathways, including AMPK/mTOR (mitogen activated protein kinase/mammalian target rapamycin), STAT3 (signal transducer and activator of transcription) and numerous factors: NF-KB (nuclear factor kappa), HIF-1 alpha (hypoxia inducible factor 1), IGF-1 (insulin-like growth factor-1), which affect cell proliferation and apoptosis. In addition, metformin eliminates CSCs (cancer stem cells) that are associated with cancer progression, metastasis and resistance to treatment. The effect of metformin in breast and endometrial cancer is favourable in the vast majority of studies. The results of studies on ovarian and cervical cancer promote metformin as a candidate in the combination treatment of these cancers. More results from meta-analyzes and clinical trials are awaited. It is clearly recognized that metformin as an antidiabetic in women with type 2 diabetes has an advantage over other antidiabetics due to its anticancer activity.
Topics: Female; Humans; Metformin; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Signal Transduction; Endometrial Neoplasms; Cell Proliferation
PubMed: 35072253
DOI: 10.5603/GP.a2021.0222 -
Current Osteoporosis Reports Dec 2023Metformin is an anti-glycemic agent, which is widely prescribed to diabetes patients. Although its alleged role on bone strength has been reported for some time, this... (Review)
Review
PURPOSE OF REVIEW
Metformin is an anti-glycemic agent, which is widely prescribed to diabetes patients. Although its alleged role on bone strength has been reported for some time, this review focuses primarily on the recent mechanistical insights of metformin on osteocytes, osteoblasts, and osteoclasts.
RECENT FINDINGS
Overall, metformin contributed to steering anabolic activity in osteocytes. It caused lower expression in osteocytes of the negative regulators of bone formation sclerostin and DKK1. Likewise, the osteoclastogenesis function of osteoblasts was also skewed towards lower RANKL and higher OPG expressions. Osteoblast lineage cells generally responded to metformin by activating bone formation parameters, such as alkaline phosphatase activity, higher expression of anabolic members of the Wnt pathway, transcription factor Runx2, bone matrix protein proteins, and subsequent mineralization. Metformin affected osteoclast formation and activity in a negative way, reducing the number of multinucleated cells in association with lower expression of typical osteoclast markers and with inhibited resorption. A common denominator studied in all three cell types is its beneficial effect on activating phosphorylated AMP kinase (AMPK) which is associated with the coordination of energy metabolism. Metformin differentially affects bone cells, shifting the balance to more bone formation. Although metformin is a drug prescribed for diabetic patients, the overall bone anabolic effects on osteocytes and osteoblasts and the anti-catabolic effect on osteoclast suggest that metformin could be seen as a promising drug in the bone field.
Topics: Humans; Osteoclasts; Osteocytes; Metformin; Osteoblasts; Bone and Bones; RANK Ligand; Cell Differentiation
PubMed: 37796390
DOI: 10.1007/s11914-023-00828-0 -
International Journal of Molecular... Apr 2023Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the...
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with infertility and metabolic disorders in reproductive-aged women. In this study, we evaluated the expression of eight genes related to endometrial function and their DNA methylation levels in the endometrium of PCOS patients and women without the disease (control group). In addition, eight of the PCOS patients underwent intervention with metformin (1500 mg/day) and a carbohydrate-controlled diet (type and quantity) for three months. Clinical and metabolic parameters were determined, and RT-qPCR and MeDIP-qPCR were used to evaluate gene expression and DNA methylation levels, respectively. Decreased expression levels of , , and genes and increased DNA methylation levels of the promoter were found in the endometrium of PCOS patients compared to controls. After metformin and nutritional intervention, some metabolic and clinical variables improved in PCOS patients. This intervention was associated with increased expression of , , and genes and reduced DNA methylation levels of the promoter in the endometrium of PCOS women. Our preliminary findings suggest that metformin and a carbohydrate-controlled diet improve endometrial function in PCOS patients, partly by modulating DNA methylation of the gene promoter and the expression of genes implicated in endometrial receptivity and insulin signaling.
Topics: Humans; Female; Adult; Metformin; Polycystic Ovary Syndrome; DNA Methylation; Endometrium; Gene Expression; Diet
PubMed: 37047828
DOI: 10.3390/ijms24076857 -
Current Problems in Cancer Aug 2023Metformin is an ancient drug for the treatment of type 2 diabetes, and many studies now suggested that metformin can be used as an adjuvant drug in the treatment of many... (Review)
Review
Metformin is an ancient drug for the treatment of type 2 diabetes, and many studies now suggested that metformin can be used as an adjuvant drug in the treatment of many types of tumors. The mechanism of action of metformin for tumor treatment mainly involves: 1. activation of AMPK signaling pathway 2. inhibition of DNA damage repair in tumor cells 3. downregulation of IGF-1 expression 4. inhibition of chemoresistance and enhancement of chemotherapy sensitivity in tumor cells 5. enhancement of antitumor immunity 6. inhibition of oxidative phosphorylation (OXPHOS). Metformin also plays an important role in the treatment of hematologic tumors, especially in leukemia, lymphoma, and multiple myeloma (MM). The combination of metformin and chemotherapy enhances the efficacy of chemotherapy, and metformin reduces the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. The purpose of this review is to summarize the anticancer mechanism of metformin and the role and mechanism of action of metformin in hematologic tumors. We mainly summarize the studies related to metformin in hematologic tumors, including cellular experiments and animal experiments, as well as controlled clinical studies and clinical trials. In addition, we also focus on the possible side effects of metformin. Although a large number of preclinical and clinical studies have been performed and the role of metformin in preventing the progression of MGUS to MM has been demonstrated, metformin has not been approved for the treatment of hematologic tumors, which is related to the adverse effects of its high-dose application. Low-dose metformin reduces adverse effects and has been shown to alter the tumor microenvironment and enhance antitumor immune response, which is one of the main directions for future research.
Topics: Animals; Humans; Metformin; Diabetes Mellitus, Type 2; Drug Repositioning; Multiple Myeloma; Hematologic Neoplasms; Tumor Microenvironment
PubMed: 37364455
DOI: 10.1016/j.currproblcancer.2023.100972 -
Journal of Experimental & Clinical... Dec 2019Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications... (Review)
Review
Growing evidence showed the increased prevalence of cancer incidents, particularly colorectal cancer, among type 2 diabetic mellitus patients. Antidiabetic medications such as, insulin, sulfonylureas, dipeptyl peptidase (DPP) 4 inhibitors and glucose-dependent insulinotropic peptide (GLP-1) analogues increased the additional risk of different cancers to diabetic patients. Conversely, metformin has drawn attention among physicians and researchers since its use as antidiabetic drug exhibited beneficial effect in the prevention and treatment of cancer in diabetic patients as well as an independent anticancer drug. This review aims to provide the comprehensive information on the use of metformin at preclinical and clinical stages among colorectal cancer patients. We highlight the efficacy of metformin as an anti-proliferative, chemopreventive, apoptosis inducing agent, adjuvant, and radio-chemosensitizer in various colorectal cancer models. This multifarious effects of metformin is largely attributed to its capability in modulating upstream and downstream molecular targets involved in apoptosis, autophagy, cell cycle, oxidative stress, inflammation, metabolic homeostasis, and epigenetic regulation. Moreover, the review highlights metformin intake and colorectal cancer risk based on different clinical and epidemiologic results from different gender and specific population background among diabetic and non-diabetic patients. The improved understanding of metformin as a potential chemotherapeutic drug or as neo-adjuvant will provide better information for it to be used globally as an affordable, well-tolerated, and effective anticancer agent for colorectal cancer.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Clinical Trials as Topic; Colorectal Neoplasms; Humans; Metformin
PubMed: 31831021
DOI: 10.1186/s13046-019-1495-2