Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner

Valaee, Shiva; Yaghoobi, Mohammad Mehdi; Shamsara, Mehdi

doi:10.1371/journal.pone.0174486

Cited by 44 publications

(44 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…50 and 100 μg/mL). These data agree with previous published studies, in which 7.8 mM glucose (corresponding to about 1.4 mg/mL) [66] was used as a non-fasting basal blood sugar level, while concentrations of 17.5, 25 and 33 mM glucose (corresponding to about 3.0, 4.5 and 6.0 mg/mL) to simulate hyperglycemic conditions [66][67][68]. Along with the extract, the most abundant identified phenolics, i.e.…”

Section: Pge Counteracts the Oxidative Stress Induced Under Hyperglycsupporting

confidence: 93%

Hypoglycemic, Antiglycation and Cytoprotective Properties of A Phenol Rich Extract from Waste Peel of <i>Punica Granatum</i> L. Var. Dente Di Cavallo DC2

Sotto¹,

Locatelli²,

Macone³

et al. 2019

Preprint

View full text Add to dashboard Cite

Pomegranate peel is a natural source of phenolics, claimed to possess healing properties, among which antioxidant and antidiabetic. In line with this evidence, the ethyl acetate PGE extract, obtained by Soxhlet from the peel of Dente di cavallo DC2 variety and characterized by a 4% amount of ellagic acid, has been studied for its hypoglycemic, antiglycation and antioxidative cytoprotective properties, in order to support a possible further nutraceutical interest. The α-amylase and α-glucosidase enzyme inhibition, interference with advanced glycation end-products (AGE) formation and metal chelating abilities were evaluated as hypoglycemic mechanisms. Also, considering that oxidative stress is associated with hyperglycemia complications, PGE antioxidant cytoprotective properties under hyperglycemic conditions were assayed. Phenolic profile was characterized by integrated chromatographic and spectrophotometric methods. Under our experimental conditions, PGE strongly inhibited the tested enzymes, especially α-glucosidase, and exerted chelating and antiglycation properties. Also, it reduced both ROS and GSH levels under hyperglycemic conditions, thus suggesting its ability to support cell functions by counteracting intracellular oxidative stress. Along with ellagic acid, rutin was the major identified flavonoid (about 4 %) of PGE. Present results suggest PGE to be a possible remedy for hyperglycemia management and encourage further studies to exploit its promising properties.

show abstract

Section: Pge Counteracts the Oxidative Stress Induced Under Hyperglycsupporting

confidence: 93%

Hypoglycemic, Antiglycation and Cytoprotective Properties of A Phenol Rich Extract from Waste Peel of <i>Punica Granatum</i> L. Var. Dente Di Cavallo DC2

Sotto¹,

Locatelli²,

Macone³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The previous study of Chang et al, suggested that metformin can reverse EMT in GC [30]. Valaee et al and Jun et al recently confirmed this effect on the GC cell line AGS [33,34]. Indeed, the treatment of AGS cells with metformin decreased the expression of β-catenin and vimentin [33] as well as matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF) [34].…”

Section: Metformin Inhibits Epithelial-to-mesenchymal Transitionmentioning

confidence: 88%

“…Valaee et al and Jun et al recently confirmed this effect on the GC cell line AGS [33,34]. Indeed, the treatment of AGS cells with metformin decreased the expression of β-catenin and vimentin [33] as well as matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF) [34]. On the contrary, the expression of E-cadherin was increased in response to metformin [33,34].…”

Section: Metformin Inhibits Epithelial-to-mesenchymal Transitionmentioning

confidence: 89%

“…On the contrary, the expression of E-cadherin was increased in response to metformin [33,34]. At functional level, metformin decreased cell viability, migration and invasive capacities [33,35].…”

Section: Metformin Inhibits Epithelial-to-mesenchymal Transitionmentioning

confidence: 97%

“…Indeed, the treatment of AGS cells with metformin decreased the expression of β-catenin and vimentin [33] as well as matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF) [34]. On the contrary, the expression of E-cadherin was increased in response to metformin [33,34]. At functional level, metformin decreased cell viability, migration and invasive capacities [33,35].…”

Section: Metformin Inhibits Epithelial-to-mesenchymal Transitionmentioning

confidence: 99%

See 2 more Smart Citations

The therapeutic potential of metformin in gastric cancer

2019

View full text Add to dashboard Cite

Metformin is a biguanide molecule used since 1957 to treat type 2 diabetes patients. In addition to its hypoglycemic effects, epidemiological studies have shown that metformin can be associated with a decrease in cancer development risk in diabetic populations. Thus, since 2005 this molecule is largely studied for its antitumoural properties in different types of cancer. The potential antitumoural effect of metformin in gastric cancer has been poorly studied. Here, we detailed the different described mechanisms implicated in the antitumoural effect of metformin in gastric cancer, from the signalling pathways to the functional effects on gastric cancer cell lines and gastric cancer stem cells.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

Metformin modulates oncogenic expression of HOTAIR gene via promoter methylation and reverses epithelial–mesenchymal transition in MDA‐MB‐231 cells

Golshan

Khaleghi

Shafiee

et al. 2020

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Epithelial–mesenchymal transition (EMT) is a biological event, which critically regulates migration and invasion of cancer cells. EMT is regulated by several protein and nonprotein factors (such as noncoding RNAs). HOTAIR is an oncogenic long noncoding RNA that stimulates EMT in cancers. In the current study, we investigated the effect of metformin on EMT behavior and HOTAIR expression in MDA‐MB‐231 breast cancer cells. The minimal effective concentrations of metformin (10 and 20 mM) were obtained by the MTT test. Cell migration and invasion in the metformin‐containing medium were assayed in the scratch assay and transwell test. Meaningful decreases in both cell migration and invasion were observed in the presence of metformin. Vimentin, snail, β‐catenin, and HOTAIR transcripts were quantified by real‐time polymerase chain reaction (PCR). Reduction in the expression of vimentin, β‐catenin, and HOTAIR was detected as the result of metformin treatment, but the snail showed a constant expression. Western blottingrevealed the downregulation of vimentin and β‐catenin proteins. HOTAIR promoter methylation pattern was also investigated in metformin‐exposed cells using bisulfite sequencing PCR which the result showed differences in the methylation profile of CpG islands between the treated and untreated cells. In conclusion, metformin modulated oncogenic expression of the HOTAIR gene in the MDA‐MB‐231 cells. This downregulation was associated with the modification of promoter methylation patterns. Since HOTAIR induces EMT in breast cancer, HOTAIR decline might be one of the mechanisms by which metformin reverses EMT.

show abstract

Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner

Cited by 44 publications

References 39 publications

Hypoglycemic, Antiglycation and Cytoprotective Properties of A Phenol Rich Extract from Waste Peel of <i>Punica Granatum</i> L. Var. Dente Di Cavallo DC2

Hypoglycemic, Antiglycation and Cytoprotective Properties of A Phenol Rich Extract from Waste Peel of <i>Punica Granatum</i> L. Var. Dente Di Cavallo DC2

The therapeutic potential of metformin in gastric cancer

Metformin modulates oncogenic expression of HOTAIR gene via promoter methylation and reverses epithelial–mesenchymal transition in MDA‐MB‐231 cells

Contact Info

Product

Resources

About