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Metformin AND AMPK

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https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#1
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#2
Safar Kheder, Karen Sisley, Sirwan Hadad, Sabapathy P Balasubramanian
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#3
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502303/-effect-of-metformin-on-proliferation-and-apoptosis-of-rat-prolactinoma-mmq-cells-and-related-mechanisms
#4
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mou, Gang Yang
Objective To investigate the effect of metformin on the cell proliferation, cell cycle and apoptosis of rat prolactinoma MMQ cells in vitro and related molecular mechanisms. Methods The MMQ cells were treated with 1.25, 2.5, 5, 10, 20 mmol/L metformin for 48 hours. CCK-8 assay was used to assess the cell proliferation ability; flow cytometry was used to analyze the cell cycle distribution and apoptosis; Western blotting was performed to detect the expressions of AMPKα1/2, p-AMPKα, mTOR, p-mTOR, insulin like growth factor 1 receptor (IGF-1R), ERK1/2, p-ERK1/2, AKT, p-AKT, P21, CDK4, cyclin D1, caspase-3, cleaved caspase-3(c-caspase-3), Bcl-2 and BAX...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28497164/metformin-prevents-ischaemic-ventricular-fibrillation-in-metabolically-normal-pigs
#5
Li Lu, Shuyu Ye, Rebecca L Scalzo, Jane E B Reusch, Clifford R Greyson, Gregory G Schwartz
AIMS/HYPOTHESIS: Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs...
May 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28496098/combined-treatment-with-metformin-and-2-deoxy-glucose-induces-detachment-of-viable-mda-mb-231-breast-cancer-cells-in-vitro
#6
Maruša Bizjak, Petra Malavašič, Klemen Dolinar, Jelka Pohar, Sergej Pirkmajer, Mojca Pavlin
Triple naegative breast cancer has an increased rate of distant metastasis and consequently poor prognosis. To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize in vivo, the viability of floating cancer cells in vitro is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494141/metformin-induces-osteoblastic-differentiation-of-human-induced-pluripotent-stem-cell-derived-mesenchymal-stem-cells
#7
Ping Wang, Tao Ma, Dong Guo, Kevin Hu, Yan Shu, Hockin H K Xu, Abraham Schneider
Metformin, a first-line anti-diabetic drug used by millions of patients has been shown to have potential osteogenic properties. The present study was performed to test the hypothesis that clinically relevant doses of metformin promote the osteogenic differentiation and mineralization of induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells (iPSC-MSCs). iPSC-MSCs were treated with metformin (10 μM) to assess cell viability, osteogenic differentiation, mineralization, and activation of the LKB1/AMP-activated protein kinase (AMPK) signaling pathway, a surrogate marker of metformin action...
May 11, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28473772/lack-of-effects-of-metformin-and-aicar-chronic-infusion-on-the-development-of-hypertension-in-dahl-salt-sensitive-rats
#8
Tengis S Pavlov, Vladislav Levchenko, Daria V Ilatovskaya, Hui Li, Oleg Palygin, Nuria M Pastor-Soler, Kenneth R Hallows, Alexander Staruschenko
In the kidney, reabsorption via the epithelial sodium channel (ENaC) is involved in long-term blood pressure control. Previously we demonstrated that ENaC hyperactivity is associated with development of salt-sensitive (SS) hypertension in Dahl SS rats. AMP-activated kinase (AMPK), playing a role in cellular energy homeostasis, has been shown to decrease ENaC activity. Here, we tested whether metformin and AICAR, two drugs that activate AMPK, affect the development of salt-induced hypertension. High salt diet significantly increased mean arterial pressure (MAP) in Dahl SS rats...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28450808/metformin-exhibits-the-anti-proliferation-and-anti-invasion-effects-in-hepatocellular-carcinoma-cells-after-insufficient-radiofrequency-ablation
#9
Qingyun Zhang, Jian Kong, Shuying Dong, Wenlei Xu, Wenbing Sun
BACKGROUND: The mechanisms and prevention of progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily investigated, therefore, new strategy needs to be investigated to prevent the process. Whether metformin could be used to inhibit the growth of HCC after insufficient RFA and further prevent the progression of residual HCC remains unclearly. METHODS: MTT assay, colony formation assay and transwell assay were used to observe the cell viability, migration and invasion...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28436023/activation-of-amp-activated-protein-kinase-by-metformin-ablates-angiotensin-ii-induced-endoplasmic-reticulum-stress-and-hypertension-in-mice-in-vivo
#10
Quanlu Duan, Ping Song, Ye Ding, Ming-Hui Zou
BACKGROUND AND PURPOSE: Metformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts blood pressure (BP)-lowering effects in patients with diabetes; however, the effects and underlying mechanisms of metformin on BP in non-diabetic condition remains to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The effects of metformin on BP were investigated in wild-type (WT, C57BL/6 J) and AMP-activated protein kinase (AMPKα2) knockout (AMPKα2(-/-) ) mice with or without Ang II-infusion...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#11
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423712/model-based-unsupervised-learning-informs-metformin-induced-cell-migration-inhibition-through-an-ampk-independent-mechanism-in-breast-cancer
#12
Arjun P Athreya, Krishna R Kalari, Junmei Cairns, Alan J Gaglio, Quin F Wills, Nifang Niu, Richard Weinshilboum, Ravishankar K Iyer, Liewei Wang
We demonstrate that model-based unsupervised learning can uniquely discriminate single-cell subpopulations by their gene expression distributions, which in turn allow us to identify specific genes for focused functional studies. This method was applied to MDA-MB-231 breast cancer cells treated with the antidiabetic drug metformin, which is being repurposed for treatment of triple-negative breast cancer. Unsupervised learning identified a cluster of metformin-treated cells characterized by a significant suppression of 230 genes (p-value < 2E-16)...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410530/metformin-attenuated-endotoxin-induced-acute-myocarditis-via-activating-ampk
#13
Gang Liu, Kejia Wu, Li Zhang, Jie Dai, Wei Huang, Ling Lin, Pu Ge, Fuling Luo, Han Lei
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28393693/update-on-the-protective-renal-effects-of-metformin-in-diabetic-nephropathy
#14
Andreas Eisenreich, Ulrike Leppert
BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy...
April 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#15
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#16
REVIEW
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael Dwinell
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential...
April 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28380462/metformin-inhibits-proliferation-and-growth-hormone-secretion-of-gh3-pituitary-adenoma-cells
#17
Jiayin An, Xiangdong Pei, Zhenle Zang, Zheng Zhou, Jintao Hu, Xin Zheng, Yin Zhang, Jiaojiang He, Lian Duan, Rufei Shen, Weihua Zhang, Feng Zhu, Song Li, Hui Yang
Metformin is an anti-hyperglycemic agent used to treat diabetes, and recent evidence suggests it has antitumor efficacy. Because growth hormone-secreting pituitary adenoma (GH-PA) patients have a high incidence of diabetes frequently treated with metformin, we assessed the antitumor effect of metformin on GH-PA. We found that metformin effectively inhibited proliferation and induced apoptosis in the GH-PA cell line GH3. We detected a decrease in mitochondrial membrane potential (MMP), an increase in expression of pro-apoptotic proteins, and a decrease in expression of an anti-apoptotic protein in metformin-treated GH3 cells, which suggests involvement of the mitochondrial-mediated apoptosis pathway...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373018/corrigendum-to-metformin-has-adenosine-monophosphate-activated-protein-kinase-ampk-independent-effects-on-lps-stimulated-rat-primary-microglial-cultures-pharmacol-rep-62-2010-827-848
#18
Krzysztof Łabuzek, Sebastian Liber, Bożena Gabryel, Bogusław Okopień
No abstract text is available yet for this article.
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#19
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor (HIF) was not involved in the down-regulation of HNF4α under hypoxic conditions...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28363500/corrigendum-to-metformin-affects-macrophages-phenotype-and-improves-the-activity-of-glutathione-peroxidase-superoxide-dismutase-catalase-and-decreases-malondialdehyde-concentration-in-a-partially-ampk-independent-manner-in-lps-stimulated-human-monocytes-macrophages
#20
Łukasz Bułdak, Krzysztof Łabuzek, Rafał Jakub Bułdak, Michał Kozłowski, Grzegorz Machnik, Sebastian Liber, Dariusz Suchy, Anna Duława-Bułdak, Bogusław Okopień
No abstract text is available yet for this article.
June 2017: Pharmacological Reports: PR
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