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https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#1
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230250/metformin-attenuates-angiotensin-ii-induced-tgf%C3%AE-1-expression-by-targeting-hepatocyte-nuclear-factor-4%C3%AE
#2
Ruifei Chen, Yenan Feng, Jimin Wu, Yao Song, Hao Li, Qiang Shen, Dan Li, Jianshu Zhang, Zhizhen Lu, Han Xiao, Youyi Zhang
BACKGROUND AND PURPOSE: Metformin, a small molecule antihyperglycaemic agent, is well-known as an AMP-activated protein kinase (AMPK) activator and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. Transforming growth factor-β1 (TGFβ1) is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms. EXPERIMENTAL APPROACH: Wild-type and AMPKα2(-/-) C57BL/6 mice were subcutaneously injected with metformin or saline and infused with AngII (3 mg kg(-1) day(-1) ) for 7 days...
February 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28230206/mirna-21-mediates-the-antiangiogenic-activity-of-metformin-through-targeting-pten-and-smad7-expression-and-pi3k-akt-pathway
#3
Mao Luo, Xiaoyong Tan, Lin Mu, Yulin Luo, Rong Li, Xin Deng, Ni Chen, Meiping Ren, Yongjie Li, Liqun Wang, Jianbo Wu, Qin Wan
Metformin, an anti-diabetic drug commonly used for type 2 diabetes therapy, is associated with anti-angiogenic effects in conditions beyond diabetes. miR-21 has been reported to be involved in the process of angiogenesis. However, the precise regulatory mechanisms by which the metformin-induced endothelial suppression and its effects on miR-21-dependent pathways are still unclear. Bioinformatic analysis and identification of miR-21 and its targets and their effects on metformin-induced antiangiogenic activity were assessed using luciferase assays, quantitative real-time PCR, western blots, scratch assays, CCK-8 assays and tubule formation assays...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#4
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28209916/diabetic-concentrations-of-metformin-inhibit-platelet-mediated-ovarian-cancer-cell-progression
#5
Rafaela Erices, Sofía Cubillos, Raúl Aravena, Felice Santoro, Monica Marquez, Renan Orellana, Carolina Ramírez, Pamela González, Patricia Fuenzalida, María Loreto Bravo, Bárbara Oliva, Sumie Kato, Carolina Ibañez, Jorge Brañes, Erasmo Bravo, Catalina Alonso, Karen García, Clemente Arab, Vicente A Torres, Alejandro S Godoy, Jaime Pereira, Galdo Bustos, Julio Cesar Cardenas, Mauricio A Cuello, Gareth I Owen
Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208582/nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users
#6
REVIEW
Fedra Luciano-Mateo, Anna Hernández-Aguilera, Noemi Cabre, Jordi Camps, Salvador Fernández-Arroyo, Jose Lopez-Miranda, Javier A Menendez, Jorge Joven
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan...
February 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28206714/opposite-effects-of-a-glucokinase-activator-and-metformin-on-glucose-regulated-gene-expression-in-hepatocytes
#7
Ziad H Al-Oanzi, Sophia Fountana, Tabassum Moonira, Susan J Tudhope, John L Petrie, Ahmed Alshawi, Gillian Patman, Catherine Arden, Helen L Reeves, Loranne Agius
AIM: Small molecule activators of glucokinase (GKAs) have been extensively explored as potential anti-hyperglycaemic drugs for type 2 diabetes (T2D). Several GKAs were remarkably effective at lowering blood glucose during early therapy but then lost their glycaemic efficacy chronically during clinical trials. We used rat hepatocytes to test the hypothesis that GKAs raise hepatocyte glucose 6-phosphate, (G6P, the glucokinase product) and down-stream metabolites with consequent repression of the liver glucokinase gene (Gck)...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28193839/metformin-promotes-amp-activated-protein-kinase-independent-suppression-of-%C3%AE-np63%C3%AE-and-inhibits-cancer-cell-viability
#8
Yong Yi, Deshi Chen, Juan Ao, Shengnan Sun, Min Wu, Xiaorong Li, Johann Bergholz, Yujun Zhang, Zhi-Xiong Xiao
The blood-glucose modifier metformin is used to treat type II diabetes and has also been shown to possess anti-cancer activities. Recent studies indicate that glucose deprivation can greatly enhance metformin-mediated inhibition of cell viability, but the molecular mechanism involved in this inhibition is unclear. In this study, we report that under glucose deprivation metformin inhibited expression of ΔNp63α, a p53 family member involved in cell adhesion pathways, resulting in disruption of cell-matrix adhesion and in subsequent apoptosis in human squamous carcinoma cells...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28193239/buformin-inhibits-the-stemness-of-erbb-2-overexpressing-breast-cancer-cells-and-premalignant-mammary-tissues-of-mmtv-erbb-2-transgenic-mice
#9
Amanda B Parris, Qingxia Zhao, Erin W Howard, Ming Zhao, Zhikun Ma, Xiaohe Yang
BACKGROUND: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28185288/metformin-effects-on-head-and-neck-squamous-carcinoma-microenvironment-window-of-opportunity-trial
#10
Joseph Curry, Jennifer Johnson, Patrick Tassone, Marina Domingo Vidal, Diana Whitaker Menezes, John Sprandio, Mehri Mollaee, Paolo Cotzia, Ruth Birbe, Zhao Lin, Kurren Gill, Elizabeth Duddy, Tingting Zhan, Benjamin Leiby, Michelle Reyzer, David Cognetti, Adam Luginbuhl, Madalina Tuluc, Ubaldo Martinez-Outschoorn
OBJECTIVE: The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY DESIGN: Window of opportunity trial of metformin between diagnostic biopsy and resection...
February 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28183460/corrigendum-to-metformin-suppresses-adipogenesis-through-both-amp-activated-protein-kinase-ampk-dependent-and-ampk-independent-mechanisms-mol-cell-endocrinol-440-15-january-2017-57-68
#11
S C Chen, R Brooks, J Houskeeper, S K Bremner, J Dunlop, B Viollet, P J Logan, I P Salt, S F Ahmed, S J Yarwood
No abstract text is available yet for this article.
March 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28178338/the-impact-of-obesity-and-adiponectin-signaling-in-patients-with-renal-cell-carcinoma-a-potential-mechanism-for-the-obesity-paradox
#12
Ryuichi Ito, Shintaro Narita, Mingguo Huang, Taketoshi Nara, Kazuyuki Numakura, Koichiro Takayama, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, Tomonori Habuchi
Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin...
2017: PloS One
https://www.readbyqxmd.com/read/28176222/saxagliptin-dapagliflozin-a-review-in-type-2-diabetes-mellitus
#13
Karly P Garnock-Jones
Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern(®)) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication...
February 7, 2017: Drugs
https://www.readbyqxmd.com/read/28174122/role-of-salt-inducible-kinase-1-in-high-glucose-induced-lipid-accumulation-in-hepg2-cells-and-metformin-intervention
#14
Yue Zhang, Hiroshi Takemori, Chang Wang, JiaHui Fu, MingWang Xu, Liang Xiong, NingXu Li, XiuYing Wen
AIMS: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis. MAIN METHODS: A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit...
February 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28163112/antidiabetic-effects-of-morus-alba-fruit-polysaccharides-on-high-fat-diet-and-streptozotocin-induced-type-2-diabetes-in-rats
#15
Yukun Jiao, Xueqian Wang, Xiang Jiang, Fansheng Kong, Shumei Wang, Chunyan Yan
ETHNOPHARMACOLOGICAL RELEVANCE: Type 2 diabetes mellitus (T2DM) is becoming a serious threat to human health. The fruit of Morus alba L. is widely used as a traditional Chinese medicine for the treatment of DM, dizziness, tinnitus, insomnia, and premature graying, as well as to protect the liver and kidneys. Several studies have demonstrated that the aqueous extracts of the roots bark, leaves, and ramuli of mulberry, which are known to contain polyphenols and polysaccharides, have antihyperglycemic and antihyperlipidemic activities...
February 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#16
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28159472/metformin-activation-of-ampk-suppresses-age-induced-inflammatory-response-in-hnscs
#17
Ming-Min Chung, Christopher J Nicol, Yi-Chuan Cheng, Kuan-Hung Lin, Yen-Lin Chen, Dee Pei, Chien-Hung Lin, Yi-Nuo Shih, Chia-Hui Yen, Shiang-Jiuun Chen, Rong-Nan Huang, Ming-Chang Chiang
A growing body of evidence suggests type 2 diabetes mellitus (T2DM) is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanisms remain unclear, T2DM may exacerbate neurodegenerative processes. AMP-activated protein kinase (AMPK) signaling is an evolutionary preserved pathway that is important during homeostatic energy biogenesis responses at both the cellular and whole-body levels. Metformin, a ubiquitously prescribed anti-diabetic drug, exerts its effects by AMPK activation...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28158902/metformin-attenuates-albumin-induced-alterations-in-renal-tubular-cells-in-vitro
#18
Soumaya Allouch, Shankar Munusamy
Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28158227/beneficial-effects-of-metformin-on-energy-metabolism-and-visceral-fat-volume-through-a-possible-mechanism-of-fatty-acid-oxidation-in-human-subjects-and-rats
#19
Ichiro Tokubuchi, Yuji Tajiri, Shimpei Iwata, Kento Hara, Nobuhiko Wada, Toshihiko Hashinaga, Hitomi Nakayama, Hiroharu Mifune, Kentaro Yamada
OBJECTIVE: Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. METHODS: In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin...
2017: PloS One
https://www.readbyqxmd.com/read/28157701/metformin-treated-cancer-cells-modulate-macrophage-polarization-through-ampk-nf-%C3%AE%C2%BAb-signaling
#20
Chi-Fu Chiang, Ting-Ting Chao, Yu-Fu Su, Chia-Chen Hsu, Chu-Yen Chien, Kuo-Chou Chiu, Shine-Gwo Shiah, Chien-Hsing Lee, Shyun-Yeu Liu, Yi-Shing Shieh
Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages...
February 1, 2017: Oncotarget
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