ArticleOncotarget2014
Metformin impairs Rho GTPase signaling to induce apoptosis in neuroblastoma cells and inhibits growth of tumors in the xenograft mouse model of neuroblastoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- The Role of Cdc42 in the Insulin and Leptin Pathways Contributing to the Development of Age-Related Obesity.Nutrients · 2023Review
- Triple Therapy with Metformin, Ketogenic Diet, and Metronomic Cyclophosphamide Reduced Tumor Growth in MYCN-Amplified Neuroblastoma Xenografts.Metabolites · 2023Article
- Article
- Effects of Monensin and Rapamycin Combination Therapy on Tumor Growth and Apoptosis in a Xenograft Mouse Model of Neuroblastoma.Antibiotics (Basel, Switzerland) · 2023Article
- Photodynamic treatment modulates various GTPase and cellular signalling pathways in Tauopathy.Small GTPases · 2022Article
- 0.5‑Gy X‑ray irradiation induces reorganization of cytoskeleton and differentiation of osteoblasts.Molecular medicine reports · 2021Article
- A Novel Alginate-Based Delivery System for the Prevention and Treatment of Pressure-Overload Induced Heart Failure.Frontiers in pharmacology · 2020Article
- Alpha-calcitonin gene-related peptide prevents pressure-overload induced heart failure: role of apoptosis and oxidative stress.Physiological reports · 2019Article
- p-21 Activated Kinase as a Molecular Target for Chemoprevention in Diabetes.Geriatrics (Basel, Switzerland) · 2018Review
- Inhibition of the RhoGTPase Cdc42 by ML141 enhances hepatocyte differentiation from human adipose-derived mesenchymal stem cells via the Wnt5a/PI3K/miR-122 pathway: impact of the age of the donor.Stem cell research & therapy · 2018Article
- Metformin and ageing: improving ageing outcomes beyond glycaemic control.Diabetologia · 2017Review
- RhoA inhibits the hypoxia-induced apoptosis and mitochondrial dysfunction in chondrocytes via positively regulating the CREB phosphorylation.Bioscience reports · 2017Article
- Model-based unsupervised learning informs metformin-induced cell-migration inhibition through an AMPK-independent mechanism in breast cancer.Oncotarget · 2017Article
- ROS Production and ERK Activity Are Involved in the Effects of d-β-Hydroxybutyrate and Metformin in a Glucose Deficient Condition.International journal of molecular sciences · 2017Article
- Interaction of the Small GTPase Cdc42 with Arginine Kinase Restricts White Spot Syndrome Virus in Shrimp.Journal of virology · 2017Article
- Cearoin Induces Autophagy, ERK Activation and Apoptosis via ROS Generation in SH-SY5Y Neuroblastoma Cells.Molecules (Basel, Switzerland) · 2017Article
- Metformin as a new anti-cancer drug in adrenocortical carcinoma.Oncotarget · 2016Article
- Cellular Stress and p53-Associated Apoptosis by Juniperus communis L. Berry Extract Treatment in the Human SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2016Article
- PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs.PPAR research · 2016Review
- Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells.Frontiers in neuroscience · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Metformin has been shown to inhibit tumor growth in xenograft rodent models of adult cancers, and various human clinical trials are in progress. However, the precise molecular mechanisms of metformin action are largely unknown. In the present study we examined the anti-tumor activity of metformin against neuroblastoma, and determined the underlying signaling mechanisms. Using human neuroblastoma xenograft mice, we demonstrated that oral administration of metformin (100 and 250 mg/kg body weight) significantly inhibited the growth of tumors. The interference of metformin in spheroid formation further confirmed the anti-tumor activity of metformin. In tumors, the activation of Rac1 (GTP-Rac1) and Cdc42 (GTP-Cdc42) was increased while RhoA activation (GTP-RhoA) was decreased by metformin. It also induced phosphorylation of JNK and inhibited the phosphorylation of ERK1/2 without affecting p38 MAP Kinase. Infection of cells by adenoviruses expressing dominant negative Rac1 (Rac1-N17), Cdc42 (Cdc42-N17) or constitutively active RhoA (RhoA-V14), or incubation of cells with pharmacological inhibitors of Rac1 (NSC23766) or Cdc42 (ML141) significantly protected neuroblastoma cells from metformin-induced apoptosis. Additionally, inhibition of JNK activity along with Rac1 or Cdc42 attenuated cytotoxic effects of metformin. These studies demonstrated that metformin impairs Rho GTPases signaling to induce apoptosis via JNK pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.