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Metformin AND AMPK

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https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#1
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29190959/effect-of-ampk-signal-pathway-on-pathogenesis-of-abdominal-aortic-aneurysms
#2
Le Yang, Lin Shen, Peixian Gao, Gang Li, Yuxiang He, Maohua Wang, Hua Zhou, Hai Yuan, Xing Jin, Xuejun Wu
Background and aims: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). Methods: AAA was induced in ApoE-/- mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190886/metformin-activates-type-i-interferon-signaling-against-hcv-via-activation-of-adenosine-monophosphate-activated-protein-kinase
#3
Wei-Lun Tsai, Tsung-Hsien Chang, Wei-Chi Sun, Hoi-Hung Chan, Chun-Ching Wu, Ping-I Hsu, Jin-Shiung Cheng, Ming-Lung Yu
Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187435/evaluating-metformin-as-a-potential-chemosensitizing-agent-when-combined-with-docetaxel-chemotherapy-in-castration-resistant-prostate-cancer-cells
#4
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. MATERIALS AND METHODS: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability...
December 2017: Anticancer Research
https://www.readbyqxmd.com/read/29186696/a-highly-sensitive-fret-biosensor-for-ampk-exhibits-heterogeneous-ampk-responses-among-cells-and-organs
#5
Yumi Konagaya, Kenta Terai, Yusuke Hirao, Kanako Takakura, Masamichi Imajo, Yuji Kamioka, Norio Sasaoka, Akira Kakizuka, Kenta Sumiyama, Tomoichiro Asano, Michiyuki Matsuda
AMP-activated protein kinase (AMPK), a master regulator of cellular metabolism, is a potential target for type 2 diabetes. Although extensive in vitro studies have revealed the complex regulation of AMPK, much remains unknown about the regulation in vivo. We therefore developed transgenic mice expressing a highly sensitive fluorescence resonance energy transfer (FRET)-based biosensor for AMPK, called AMPKAR-EV. AMPKAR-EV allowed us to readily examine the role of LKB1, a canonical stimulator of AMPK, in drug-induced activation and inactivation of AMPK in vitro...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29170419/pdgfr-signaling-mediates-hyperproliferation-and-fibrotic-responses-of-subsynovial-connective-tissue-cells-in-idiopathic-carpal-tunnel-syndrome
#6
Yuki Saito, Takako Chikenji, Yasuhiro Ozasa, Mineko Fujimiya, Toshihiko Yamashita, Anne Gingery, Kousuke Iba
Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in carpal tunnel syndrome (CTS). Identification of molecular targets and anti-fibrotic therapies could provide new treatment strategies for CTS. The contribution of SSCT cells to fibrosis and the signaling pathways that initiate and aggravate fibrosis in CTS remain unknown. Here we report that platelet-derived growth factor receptor alpha (PDGFRα) positive ( + ) cells accumulate in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in increased proliferation of PDGFRα+ cells via PI3K/Akt signaling pathway...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#7
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162538/metformin-promotes-the-proliferation-and-differentiation-of-murine-preosteoblast-by-regulating-the-expression-of-sirt6-and-oct4
#8
Wei Mu, Zhuoran Wang, Chuanyu Ma, Yunyun Jiang, Nannan Zhang, Kaiqiang Hu, Liyuan Li, Zhao Wang
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
November 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29142469/hypothermic-machine-perfusion-with-metformin-university-of-wisconsin-solution-for-ex-vivo-preservation-of-standard-and-marginal-liver-grafts-in-a-rat-model
#9
Yi-Chao Chai, Guo-Xin Dang, Hai-Qi He, Jian-Hua Shi, Hong-Ke Zhang, Rui-Tao Zhang, Bo Wang, Liang-Shuo Hu, Yi Lv
AIM: To compare the effect of University of Wisconsin (UW) solution with or without metformin, an AMP-activated protein kinase (AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion (HMP). METHODS: Eighteen young (4 mo old) and 18 aged (17 mo old) healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group (UWP), and UW solution with metformin perfusion group (MUWP)...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29128163/depsidone-and-xanthones-from-garcinia-xanthochymus-with-hypoglycemic-activity-and-the-mechanism-of-promoting-glucose-uptake-in-l6-myotubes
#10
Yunfang Li, Ping Zhao, Yu Chen, Yanze Fu, Kuan Shi, Liu Liu, Hui Liu, Mingrui Xiong, Qing-Hua Liu, Guangzhong Yang, Yuxiu Xiao
Garcinia xanthochymus is a widely used folk medicine in southwestern China. Previous studies indicated it possesses potential anti-diabetic activities both in vitro (Fu et al., 2014; Nguyen et al., 2017) and in vivo (Shivanand et al., 2017). To discover bioactive ingredients from it and unveil their mechanism of action against diabetes, the present study was designed to isolate constituents from extract of G. xanthochymus, determine their structures, screen their activities and investigate mechanism of action of the active substances...
November 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29126698/hybrid-drug-combination-combination-of-ferulic-acid-and-metformin-as-anti-diabetic-therapy
#11
REVIEW
Rakesh Nankar, P K Prabhakar, Mukesh Doble
BACKGROUND AND PURPOSE: Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin...
October 24, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29122080/role-of-adenosine-monophosphate-activated-protein-kinase-on-cell-migration-matrix-contraction-and-matrix-metalloproteinase-1-and-matrix-metalloproteinase-2-production-in-nasal-polyp-derived-fibroblasts
#12
Ji-Young Um, Seoung-Ae Lee, Joo-Hoo Park, Jae-Min Shin, Il-Ho Park, Heung-Man Lee
PURPOSE: Activation of adenosine monophosphate-activated protein kinase (AMPK) by metformin, as a master regulator of metabolism, is involved in airway tissue remodeling. Here, we investigated the physical role of AMPK on cell migration, matrix contraction, and the production of matrix metalloproteinases (MMP) in nasal polyp-derived fibroblasts (NPDF). METHODS: Primary NPDFs from six patients with chronic rhinosinusitis and nasal polyps were isolated and cultured...
November 1, 2017: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29111280/akt-activation-a-potential-strategy-to-ameliorate-insulin-resistance
#13
REVIEW
Zhengyi Zhang, Huadong Liu, Jiankang Liu
Insulin resistance is a hallmark of type 2 diabetes and obesity while the mechanism remains unclear. Current therapy to treat type 2 diabetes is metformin, the 5'-monophosphate-activated protein kinase (AMPK) activator, owing to the ability to augment peripheral glucose uptake. However, metformin also displays limitations, as AMPK activation remains intact and regular in most type 2 diabetes and metformin does not seem to facilitate peripheral insulin resistance. Evidence has shown that PI3K-Akt/PKB pathway could be induced via insulin and act as an important effector...
October 27, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29106036/inhibition-of-mitochondrial-complex-i-improves-glucose-metabolism-independently-of-ampk-activation
#14
Wo-Lin Hou, Jun Yin, Miriayi Alimujiang, Xue-Ying Yu, Li-Gen Ai, Yu-Qian Bao, Fang Liu, Wei-Ping Jia
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29100387/metabolic-modulation-of-ewing-sarcoma-cells-inhibits-tumor-growth-and-stem-cell-properties
#15
Atreyi Dasgupta, Matteo Trucco, Nino Rainusso, Ronald J Bernardi, Ryan Shuck, Lyazat Kurenbekova, David M Loeb, Jason T Yustein
Ewing sarcoma (EWS) is a highly aggressive and metabolically active malignant tumor. Metabolic activity can broadly be characterized by features of glycolytic activity and oxidative phosphorylation. We have further characterized metabolic features of EWS cells to identify potential therapeutic targets. EWS cells had significantly more glycolytic activity compared to their non-malignant counterparts. Thus, metabolic inhibitors of glycolysis such as 2-deoxy-D-glucose (2DG) and of the mitochondrial respiratory pathway, such as metformin, were evaluated as potential therapeutic agents against a panel of EWS cell lines in vitro...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099085/eburicoic-acid-a-triterpenoid-compound-from-antrodia-camphorata-displays-antidiabetic-and-antihyperlipidemic-effects-in-palmitate-treated-c2c12-myotubes-and-in-high-fat-diet-fed-mice
#16
Cheng-Hsiu Lin, Yueh-Hsiung Kuo, Chun-Ching Shih
This study was designed to investigate the antidiabetic and antihyperlipidemic effects and mechanisms of eburicoic acid (TRR); one component of Antrodia camphorata in vitro and in an animal model for 14 weeks. Expression levels of membrane glucose transporter type 4 (GLUT4); phospho-5'-adenosine monophosphate-activated protein kinase (AMPK)/total AMPK; and phospho-Akt/total-Akt in insulin-resistant C2C12 myotube cells were significantly decreased by palmitate; and such decrease was prevented and restored by TRR at different concentrations...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29094287/targeting-ampk-mtor-and-%C3%AE-catenin-by-combined-metformin-and-aspirin-therapy-in-hcc-an-appraisal-in-egyptian-hcc-patients
#17
Doaa Ali Abdelmonsif, Ahmed S Sultan, Wessam F El-Hadidy, Dina Mohamed Abdallah
BACKGROUND: Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality, both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC, although the mechanism of this effect is not fully elucidated. OBJECTIVE: The current work aimed to investigate the possibility of targeting AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and β-catenin proteins through combined metformin/aspirin treatment in the HepG2 cell line, and to explore such molecular targets in Egyptian HCC patients...
November 1, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29080400/aging-and-stem-cell-therapy-ampk-as-an-applicable-pharmacological-target-for-rejuvenation-of-aged-stem-cells-and-achieving-higher-efficacy-in-stem-cell-therapy
#18
REVIEW
Mohammadhossein Khorraminejad-Shirazi, Mohammad Farahmandnia, Bahareh Kardeh, Alireza Estedlal, Sina Kardeh, Ahmad Monabati
In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy...
October 19, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29080083/evaluation-of-metformin-effects-in-the-chronic-phase-of-spontaneous-seizures-in-pilocarpine-model-of-temporal-lobe-epilepsy
#19
Soraya Mehrabi, Nima Sanadgol, Mahmood Barati, Ali Shahbazi, Gelareh Vahabzadeh, Mitra Barzroudi, Morteza Seifi, Mazaher Gholipourmalekabadi, Fereshteh Golab
Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB)...
October 27, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29073599/combination-of-solamargine-and-metformin-strengthens-igfbp1-gene-expression-through-inactivation-of-stat3-and-reciprocal-interaction-between-foxo3a-and-sp1
#20
Qing Tang, Fang Zheng, JingJing Wu, Qian Xiao, Liuning Li, Swei Sunny Hann
BACKGROUND/AIMS: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined...
October 27, 2017: Cellular Physiology and Biochemistry
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