Metformin Increases Exosome Biogenesis and Secretion in U87 MG Human Glioblastoma Cells: A Possible Mechanism of Therapeutic Resistance

Soraya, Hamid; Sani, Neda Abbaspour; Jabbari, Nassrollah; Rezaie, Jafar

doi:10.1016/j.arcmed.2020.10.007

Cited by 52 publications

(33 citation statements)

References 68 publications

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“…In previous studies, it was shown that metformin has cytotoxicity and decreases the viability of glioblastoma cells, a promising biguanide with pronounced antitumor activity (Al Hassan et al, 2018). Furthermore, Soraya et al (2021) demonstrated that metformin significantly decreased the expression of miR-21, miR-155, and miR-182, indicating suppression of oncogenesis in glioblastoma cells. In addition, confirm metformin increased the exosome biogenesis and secretion in glioblastoma cells.…”

Section: Discussionmentioning

confidence: 96%

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors

Gareev

Beylerli

Liang

et al. 2021

Front. Cell Dev. Biol.

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Brain tumors in children and adults are challenging tumors to treat. Malignant primary brain tumors (MPBTs) such as glioblastoma have very poor outcomes, emphasizing the need to better understand their pathogenesis. Developing novel strategies to slow down or even stop the growth of brain tumors remains one of the major clinical challenges. Modern treatment strategies for MPBTs are based on open surgery, chemotherapy, and radiation therapy. However, none of these treatments, alone or in combination, are considered effective in controlling tumor progression. MicroRNAs (miRNAs) are 18–22 nucleotide long endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level by interacting with 3′-untranslated regions (3′-UTR) of mRNA-targets. It has been proven that miRNAs play a significant role in various biological processes, including the cell cycle, apoptosis, proliferation, differentiation, etc. Over the last decade, there has been an emergence of a large number of studies devoted to the role of miRNAs in the oncogenesis of brain tumors and the development of resistance to radio- and chemotherapy. Wherein, among the variety of molecules secreted by tumor cells into the external environment, extracellular vesicles (EVs) (exosomes and microvesicles) play a special role. Various elements were found in the EVs, including miRNAs, which can be transported as part of these EVs both between neighboring cells and between remotely located cells of different tissues using biological fluids. Some of these miRNAs in EVs can contribute to the development of resistance to radio- and chemotherapy in MPBTs, including multidrug resistance (MDR). This comprehensive review examines the role of miRNAs in the resistance of MPBTs (e.g., high-grade meningiomas, medulloblastoma (MB), pituitary adenomas (PAs) with aggressive behavior, and glioblastoma) to chemoradiotherapy and pharmacological treatment. It is believed that miRNAs are future therapeutic targets in MPBTs and such the role of miRNAs needs to be critically evaluated to focus on solving the problems of resistance to therapy this kind of human tumors.

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Section: Discussionmentioning

confidence: 96%

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors

Gareev

Beylerli

Liang

et al. 2021

Front. Cell Dev. Biol.

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“…Exosomes were isolated from tumour cell line to cross the blood-brain barrier [55]. Similarly, exosome isolation kit was used (EX01-8) in a study on metformin that increased exosome biogenesis and secretion in U87MG human glioblastoma cells: a possible mechanism of therapeutic resistance [56]. Patented and commercialized products like qEV (IZON), exopure™ (bio vision) and exo-spin™ columns (CELL guidance system) have been used in studies for the isolation [54].…”

Section: Isolation and Purification Methods For Exosome In Brain Diseasesmentioning

confidence: 99%

Exosomes as cell-derivative carriers in the diagnosis and treatment of central nervous system diseases

Shetgaonkar

Marques

DCruz³

et al. 2021

Drug Deliv. and Transl. Res.

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Exosomes are extracellular vesicles with the diameter ranging from 50 to 100 nm and are found in different body fluids such as blood, cerebrospinal fluid (CSF), urine and saliva. Like in case of various diseases, based on the parent cells, the content of exosomes (protein, mRNA, miRNA, DNA, lipids and metabolites) varies and thus can be utilized as potential biomarker for diagnosis and prognosis of the brain diseases. Furthermore, utilizing the natural potential exosomes to cross the blood–brain barrier and by specifically decorating it with the ligand as per the desired brain sites therapeutics can be delivered to brain parenchyma. This review article conveys the importance of exosomes and their use in the treatment and diagnosis of brain/central nervous system diseases. Graphical abstract

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“…Another interesting study found that metformin, a common drug used to treat diabetes, increased the production of human glioblastoma cell (U87 MG) exosomes. Metformin reduces the activity of U87 MG human glioblastoma cells and inhibits the expression of cancer-promoting genes related to angiogenesis, carcinogenesis and chemoresistance molecules ( 53 ). However, previous reports found that the expression of CD63, Alix, and Rab27A decreased in human endothelial progenitor cells (EPCs) cultured in diabetic serum ( 54 ).…”

Section: Effects Of Exosomes In Diabetes Mellitusmentioning

confidence: 99%

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

Chen

Wang

et al. 2021

Front. Endocrinol.

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Diabetic vascular complications (DVC) including macrovascular and microvascular lesions, have a significant impact on public health, and lead to increased patient mortality. Disordered intercellular cascades play a vital role in diabetic systemic vasculopathy. Exosomes participate in the abnormal signal transduction of local vascular cells and mediate the transmission of metabolic disorder signal molecules in distant organs and cells through the blood circulation. They can store different signaling molecules in the membrane structure and release them into the blood, urine, and tears. In recent years, the carrier value and therapeutic effect of exosomes derived from stem cells have garnered attention. Exosomes are not only a promising biomarker but also a potential target and tool for the treatment of DVC. This review explored changes in the production process of exosomes in the diabetic microenvironment and exosomes’ early warning role in DVC from different systems and their pathological processes. On the basis of these findings, we discussed the future direction of exosomes in the treatment of DVC, and the current limitations of exosomes in DVC research.

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Metformin Increases Exosome Biogenesis and Secretion in U87 MG Human Glioblastoma Cells: A Possible Mechanism of Therapeutic Resistance

Cited by 52 publications

References 68 publications

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors

The Role of MicroRNAs in Therapeutic Resistance of Malignant Primary Brain Tumors

Exosomes as cell-derivative carriers in the diagnosis and treatment of central nervous system diseases

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

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