Mini-Special Issue paper Management of diabetic patients with hypoglycemic agents Metformin and its clinical use: new insights for an old drug in clinical practice

Cicero, Arrigo F G; Tartagni, E.; Ertek, Sibel

doi:10.5114/aoms.2012.31622

Cited by 69 publications

(31 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This drug has shown beneficial effects in suppressing the intestinal absorption of glucose (17), reducing cardiovascular risk (19), reducing the risk of lactic acidosis compared with other biguanides (20), in addition to anti-neoplastic activity in vitro and in vivo (49,50). Numerous studies have demonstrated the anti-tumor effect of metformin in cancer progression (6,15,51–53).…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review

et al. 2016

View full text Add to dashboard Cite

Metformin is commonly used for treating type 2 diabetes, and may also reduce cancer risk. Previous studies have demonstrated the association between metformin use and a decreased risk of head and neck cancer. Therefore, the aim of the present systematic review was to summarize the available literature on the in vitro anti-tumor effects of metformin on head and neck squamous cell carcinoma (HNSCC). Research studies were obtained from Cochrane Library, Embase, LILACS, MEDLINE and PubMed databases, without time or language restrictions. Only in vitro studies analyzing the effects of metformin on HNSCC cell lines were included. The authors methodically appraised all the selected studies according to the Grading of Recommendations Assessment, Development and Evaluation method to make a judgment of the evidence quality. Of the 388 identified reports, 11 studies met the inclusion criteria and were used for qualitative analysis. These studies demonstrated that metformin is important in inhibiting cell proliferation, inducing G0/G1 cell cycle arrest and apoptosis, and in regulating proteins involved in carcinogenesis pathways, which corroborates its potential in vitro anti-tumor effects. The present systematic review highlights the biological mechanisms of metformin used alone or together with traditional therapies for cancer. Though very limited, currently available preclinical evidence shows that metformin exerts a potential effect on head and neck carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Ongoing clinical trials suggest that statins, fibrates, and other lipid-lowering medicines may lead to improvements in liver biochemistry and histology in patients with NAFLD/NASH, although the potential side effects remain unclear (Dima et al 2012). Metformin, the generally recommended first-line treatment for type 2 diabetes, was also found to be effective in the treatment of NAFLD (Cicero, et al 2012). However, Weickert, et al reported that metformin might lead to suppression of serum androgen levels in patients with polycystic ovarian syndrome (PCOS) (Weickert, et al 2012).…”

Section: Part I Androgen/ar Signaling In Non-cancerous Liver Diseasesmentioning

confidence: 99%

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

Lung¹,

Lai²,

Yeh³

et al. 2014

Endocrine-Related Cancer

136

114

View full text Add to dashboard Cite

Summary Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of non-cancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.

show abstract

“…It is currently undergoing extensive evaluation for treatment of some cancers and other illnesses 4, 5 . Extensive physiological and biochemical studies have identified a large number of indirect targets, including AMP-activated kinase 6 , the LKB1 master kinase 7 , and mTOR 8 that are influenced by a relatively limited number of direct targets.…”

Section: Introductionmentioning

confidence: 99%

A Structural Basis for Biguanide Activity

et al. 2017

View full text Add to dashboard Cite

Metformin is the most commonly prescribed treatment for Type II diabetes and related disorders, however molecular insights into its mode(s) of action have been limited by an absence of structural data. Structural considerations along with an increasing body of literature demonstrating its effects on one-carbon metabolism suggest the possibility of folate mimicry and anti-folate activity. Motivated by increasing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides: phenformin, buformin, and metformin and E. coli dihydrofolate reductase (ecDHFR) based on NMR, crystallographic and molecular modeling studies. Inter-ligand Overhauser effects indicate that metformin can form ternary complexes with p-aminobenzoyl-L-glutamate (pABG) as well as other ligands that occupy the region of the folate binding site that interacts with pABG, however DHFR inhibition is not cooperative. The biguanides inhibit the activity of ecDHFR competitively, with the phenformin inhibition constant 100-fold lower than that of metformin. This inhibition may be significant at concentrations present in the gut of treated individuals, and inhibition of DHFR in intestinal mucosal cells may also occur if accumulated levels are sufficient. Perturbation of folate homeostasis can alter the pyridine nucleotide redox ratios that are important regulators of cellular metabolism.

show abstract

Mini-Special Issue paper Management of diabetic patients with hypoglycemic agents Metformin and its clinical use: new insights for an old drug in clinical practice

Cited by 69 publications

References 132 publications

Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review

Anti-tumor effects of metformin on head and neck carcinoma cell lines: A systematic review

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

A Structural Basis for Biguanide Activity

Contact Info

Product

Resources

About