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https://www.readbyqxmd.com/read/29328467/aspirin-and-metformin-exhibit-antitumor-activity-in-murine-breast-cancer
#1
Maoyuan Zhao, Yuyi Wang, Chi Du, Yanyang Liu, Nan Zhang, Feng Luo
Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-β). In the present study, we report a new link between aspirin, metformin, TGF-β1 and murine breast cancer inhibition...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326107/tcf7l2-genetic-variation-augments-incretin-resistance-and-influences-response-to-a-sulfonylurea-and-metformin-the-study-to-understand-the-genetics-of-the-acute-response-to-metformin-and-glipizide-in-humans-sugar-mgh
#2
Shylaja Srinivasan, Varinderpal Kaur, Bindu Chamarthi, Katherine R Littleton, Ling Chen, Alisa K Manning, Jordi Merino, Melissa K Thomas, Margo Hudson, Allison Goldfine, Jose C Florez
OBJECTIVE: The rs7903146 T allele in transcription-factor-7-like-2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. RESEARCH DESIGN AND METHODS: We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after one dose of glipizide (5 mg) on visit 1, and a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days...
January 11, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#3
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29303360/flaxseed-lignans-enhance-the-cytotoxicity-of-chemotherapeutic-agents-against-breast-cancer-cell-lines-mda-mb-231-and-skbr3
#4
Yunyun Di, Franklyn De Silva, Edward S Krol, Jane Alcorn
Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve treatment response, survival rates, and quality of life of breast cancer patients. This study investigated the combination of flaxseed lignans (Secoisolariciresinol and Enterolactone) with classic chemotherapeutic agents (Docetaxel, Doxorubicin, and Carboplatin) with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231...
January 5, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29290922/gestational-diabetes-from-a-to-z
#5
REVIEW
AbdelHameed Mirghani Dirar, John Doupis
Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus (T2DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia...
December 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/29286158/metformin-inhibits-hacat-cell-viability-via-the-mir-21-pten-akt-signaling-pathway
#6
Yue Deng, Weiyuan Ma
Substantial preclinical evidence has indicated out a direct anti‑proliferation effect of metformin on various solid tumors; however, further and more detailed exploration into its molecular mechanism remains to be performed. The present study aimed to investigate the effect of metformin on cell viability and its underlying mechanism, in the cultured human skin keratinocyte cell line, HaCaT. In addition, it aimed to clarify the role of the microRNA-21(miR-21)/phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase 1 (Akt) signaling pathway, which has been hypothesized to be involved in the molecular mechanism of this drug...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29286156/metformin-induced-activation-of-ampk-inhibits-the-proliferation-and-migration-of-human-aortic-smooth-muscle-cells-through-upregulation-of-p53-and-ifi16
#7
Biao Hao, Yan Xiao, Fang Song, Xiangshu Long, Jing Huang, Maobo Tian, Shiyan Deng, Qiang Wu
The proliferation and migration of vascular smooth muscle cells are significant in the development and progression of atherosclerosis and plaque rupture. Metformin is a widely used antidiabetic drug, which has been reported to inhibit cell growth and migration. The antiproliferative and antimigratory effects of metformin have been attributed to 5' adenosine monophosphate-activated protein kinase (AMPK) activation. The purpose of the present study was to investigate the effects of metformin on primary human aortic muscle cells (HASMCs) in vitro and to clarify the underlying mechanism...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285837/the-new-metformin-derivative-hl156a-prevents-oral-cancer-progression-by-inhibiting-the-igf-akt-mtor-pathways
#8
Thuy Giang Lam, Yun Soo Jeong, Soo-A Kim, Sang-Gun Ahn
Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#9
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274299/anti-proliferative-effect-of-rosiglitazone-in-the-human-t-lymphocyte-leukaemia-cell-line-jurkat-cells
#10
Rui Wei, Fei Yu, Jin Yang, Hongwei Gao, Haining Wang, Tianpei Hong
Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in various types of human cancer cells including leukaemia cells, and activation of PPARγ can inhibit cancer cell growth. However, whether PPARγ is expressed in Jurkat cells, a human T-lymphocyte leukaemia cell line, and whether activation of PPARγ affects cell biological behaviours remains to be clarified. In this study, we investigated the effect of a PPARγ activator rosiglitazone, under clinically relevant pharmacological concentrations, on the growth and apoptosis of Jurkat cells in vitro and explored the possible mechanism...
December 23, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29248761/low-dose-metformin-exposure-causes-changes-in-expression-of-endocrine-disruption-associated-genes
#11
Nicholas J Niemuth, Rebecca D Klaper
The presence of intersex fish in watersheds around the world is a warning of the presence of anthropogenic endocrine-disrupting compounds (EDCs) being deposited into the aquatic environment. The anti-diabetic drug metformin is among the most prevalent and ubiquitous of the myriad pharmaceuticals found in wastewater effluent and watersheds worldwide. In addition to its prescription for type-2 diabetes, metformin is indicated as a treatment in cancers and the endocrine disorder polycystic ovarian syndrome (PCOS)...
December 8, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29248426/pharmacological-evidence-that-metformin-blocks-the-vasopressor-responses-mediated-by-stimulation-of-%C3%AE-1-and-%C3%AE-2-adrenoceptors-in-pithed-rats
#12
Saúl Huerta de la Cruz, Grecia J Medina-Terol, Jesús H Beltrán-Ornelas, Carolina B Gomez, Yaltzir Morato-Valderrama, Araceli Sánchez-López, David Centurión
It has been reported that metformin reduces blood pressure although the mechanisms have not been described. Indeed, several mechanisms could be implicated including the interaction with α-adrenoceptors or inhibition of sympathetic outflow. Therefore, this study was designed to determine the capability of metformin to block the vasopressor responses induced by α1/2-adrenoceptor agonists or selective electrical stimulation of sympathetic outflow. For this purpose, Wistar male rats were anesthetized, pithed and cannulated for selective preganglionic stimulation of the vasopressor sympathetic outflow or drugs administration...
December 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29246951/metformin-mediates-protection-against-legionella-pneumonia-through-activation-of-ampk-and-mitochondrial-reactive-oxygen-species
#13
Chiaki Kajiwara, Yu Kusaka, Soichiro Kimura, Tetsuo Yamaguchi, Yuta Nanjo, Yoshikazu Ishii, Heiichiro Udono, Theodore J Standiford, Kazuhiro Tateda
In Legionella pneumophila infection, macrophages play a critical role in the host defense response. Metformin, an oral drug for type 2 diabetes, is attracting attention as a new supportive therapy against a variety of diseases, such as cancer and infectious diseases. The novel mechanisms for metformin actions include modulation of the effector functions of macrophages and other host immune cells. In this study, we have examined the effects of metformin on L. pneumophila infection in vitro and in vivo. Metformin treatment suppressed growth of L...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29241458/inhibition-of-the-igf-signaling-pathway-reverses-cisplatin-resistance-in-ovarian-cancer-cells
#14
Juan Du, Hui-Rong Shi, Fang Ren, Jing-Lu Wang, Qing-Hua Wu, Xia Li, Rui-Tao Zhang
BACKGROUND: This study was aimed at investigating whether metformin can reverse the resistance of ovarian cancer cells to cisplatin and exploring the underlying mechanism. METHODS: Ovarian cancer cell proliferation in vitro was evaluated using a CCK-8 assay. The resistance index of platinum-resistant ovarian cancer cells was determined and cell cycle and apoptosis rate determined by annexin V/propidium iodide double-staining in CP70 cells. Western blotting was used to determine IGF1, IGF1R, AKT, p-IGF1, p-IGF1R, p-AKT, and MRP2 levels in cells treated with different concentrations of metformin and LY29400, an inhibitor of the insulin-like growth factor pathway...
December 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29236753/effects-of-genetic-polymorphisms-on-the-oct1-and-oct2-mediated-uptake-of-ranitidine
#15
Marleen Julia Meyer, Tina Seitz, Jürgen Brockmöller, Mladen Vassilev Tzvetkov
BACKGROUND: Ranitidine (Zantac®) is a H2-receptor antagonist commonly used for the treatment of acid-related gastrointestinal diseases. Ranitidine was reported to be a substrate of the organic cation transporters OCT1 and OCT2. The hepatic transporter OCT1 is highly genetically variable. Twelve major alleles confer partial or complete loss of OCT1 activity. The effects of these polymorphisms are highly substrate-specific and therefore difficult to predict. The renal transporter OCT2 has a common polymorphism, Ala270Ser, which was reported to affect OCT2 activity...
2017: PloS One
https://www.readbyqxmd.com/read/29235180/the-effects-of-hypoglycemia-and-weight-loss-of-total-lignans-from-fructus-arctii-in-kkay-mice-and-its-mechanisms-of-the-activity
#16
Yingying Gao, Chenchen Gu, Kai Wang, Haiying Wang, Kefeng Ruan, Zhaohui Xu, Yi Feng
Fructus Arctii (great burdock achene) is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is included in the Chinese pharmacopoeia. It has been reported that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. This study aimed to investigate antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous Type 2 diabetic rodent model that exhibits marked obesity. In this study, KKAy mice were gavaged once daily with solvents (0...
December 13, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29231260/metformin-inhibits-tumorigenesis-in-hbv-induced-hepatocellular-carcinoma-by-suppressing-hulc-overexpression-caused-by-hbx
#17
Zhen Jiang, Haichao Liu
BACKGROUND: We aimed to understand whether metformin imposes the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. METHOD: Luciferase assay, RT-PCR and western-blot, MTT and flow cytometry analysis were performed to understand and the mechanism, by which metformin enhance the inhibitory effect on the HBV-associated tumorigenesis by regulating the HULC and its downstream signaling pathway. RESULT: HBX promoted viability of three types of cell lines, while metformin inhibited apoptosis of above two cells...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29228667/metformin-ameliorates-sepsis-induced-brain-injury-by-inhibiting-apoptosis-oxidative-stress-and-neuroinflammation-via-the-pi3k-akt-signaling-pathway
#18
Guangming Tang, Huiyun Yang, Jing Chen, Mengrao Shi, Lingqing Ge, Xuhua Ge, Guoji Zhu
Sepsis-induced brain injuries increase mortality, morbidity, cognitive impairment and lack of effective therapeutic treatment. Previous studies have suggested that metformin provides neuroprotective effects against ischemia, brain trauma and other brain damage, but whether metformin protects a septic brain remains unknown. Thus, the aim of this study is to investigate the possible effects and the mechanism of metformin against septic brain damage using the cecal ligation and puncture (CLP) model. Mice were randomly divided into five groups: the Sham group, CLP group, CLP+ Met group, CLP+ vehicle group and CLP+ Met+ LY group...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228440/metformin-regulates-tight-junction-of-intestinal-epithelial-cells-via-mlck-mlc-signaling-pathway
#19
H-Y Zhou, H Zhu, X-M Yao, J-P Qian, J Yang, X-D Pan, X-D Chen
OBJECTIVE: To observe the effect of metformin on the tight junction of intestinal epithelial cells and its relevant mechanism. MATERIALS AND METHODS: Caco-2 cell monolayers were incubated with or without tumor necrosis factor-α (TNF-α) (10 ng/mL) in the absence or presence of indicated concentrations of metformin. Transepithelial electrical resistance (TEER) was measured at various time points. Caco-2 cell permeability was assessed using fluorescein permeability test...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29215608/h19-lncrna-alters-methylation-and-expression-of-hnf4%C3%AE-in-the-liver-of-metformin-exposed-fetuses
#20
Jie Deng, Martin Mueller, Tingting Geng, Yuanyuan Shen, Ya Liu, Peng Hou, Ramanaiah Ramillapalli, Hugh S Taylor, Michael Paidas, Yingqun Huang
Metformin is the most widely used anti-diabetic medication worldwide. However, human and animal studies suggest that prenatal metformin exposure may increase the risk of metabolic disorders in adult offspring, yet the underpinning mechanism remains unclear. Here we report that metformin-exposed mouse fetuses exhibit elevated expression of the H19 long noncoding RNA, which induces hypomethylation and increased expression of hepatocyte nuclear factor 4α (HNF4α). As a transcription factor essential for morphological and functional differentiation of hepatocytes, HNF4α also has an indispensable role in the regulation of expression of gluconeogenic genes...
December 7, 2017: Cell Death & Disease
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