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Metformin breast cancer

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https://www.readbyqxmd.com/read/29416762/metformin-synergistically-suppress-tumor-growth-with-doxorubicin-and-reverse-drug-resistance-by-inhibiting-the-expression-and-function-of-p-glycoprotein-in-mcf7-adr-cells-and-xenograft-models
#1
Ying Li, Meng Wang, Pei Zhi, Jian You, Jian-Qing Gao
Acquired resistance to chemo-drugs remains a major obstacle to successful cancer therapy. Metformin, a well-documented drug for treating type II diabetes, was recently proposed as a novel agent for tumor treatment. In this study, we found that metformin suppressed MCF7/ADR, a doxorubicin-resistant breast cancer cell line, and acted synergistically with doxorubicin by reversing drug-resistant phenotypes both in vitro and in vivo. Metformin alone dose-dependently inhibited tumor growth, especially the stressful tumor microenvironment of glucose deficiency, and the cytotoxicity of metformin was markedly enhanced by increasing ROS production and ATP depletion...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397734/unique-features-of-metformin-a-combined-experimental-theoretical-and-simulation-study-of-its-structure-dynamics-and-interaction-energetics-with-dna-grooves
#2
Sayantan Mondal, Rudra Narayan Samajdar, Saumyak Mukherjee, Aninda Jiban Bhattacharyya, Biman Bagchi
There are certain small molecules that exhibit extraordinarily diverse biological activities. Metformin is one of them. It is widely used as anti-diabetic drug for type-two diabetes. Recent evidences of its role in anti-tumour activities and increasing the survival rates of cancer patients (namely colorectal, breast, pancreas and prostate cancer) are emerging. However, theoretical studies of structure and dynamics of metformin have not yet been fully explored. In this work, we investigate the characteristic structural and dynamical features of three mono-protonated forms of metformin hydrochloride with the help of experiments, quantum chemical calculations and atomistic molecular dynamics simulations...
February 3, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29397517/do-mcf7-cells-cope-with-metformin-treatment-under-energetic-stress-in-low-glucose-conditions
#3
Irem Dogan Turacli, Haldun Umudum, Arzu Pampal, Tuba Candar, Lara Kavasoglu, Yaren Sari
There is a growing body of evidence about metformin being effective in cancer therapy. Despite controversies about the ways of its effectiveness, several ongoing clinical trials are evaluating the drug when used as an adjuvant or a neo-adjuvant agent. We aimed to investigate metformin's effects on proliferation, metastasis, and hormone receptor expressions in breast cancer cell line MCF-7 incubated in two different glucose conditions. MCF-7 cells were incubated in high or low glucose media and treated with various doses of metformin...
February 3, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29392539/pre-clinical-effects-of-metformin-and-aspirin-on-the-cell-lines-of-different-breast-cancer-subtypes
#4
Maria Eduarda Azambuja Amaral, Laura Roesler Nery, Carlos Eduardo Leite, Walter Filgueira de Azevedo Junior, Maria Martha Campos
Background Breast cancer is highly prevalent among women worldwide. It is classified into three main subtypes: estrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+), and triple negative breast cancer (TNBC). This study has evaluated the effects of aspirin and metformin, isolated or in a combination, in breast cancer cells of the different subtypes. Methods The breast cancer cell lines MCF-7, MDA-MB-231, and SK-BR-3 were treated with aspirin and/or metformin (0.01 mM - 10 mM); functional in vitro assays were performed...
February 2, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#5
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29328467/aspirin-and-metformin-exhibit-antitumor-activity-in-murine-breast-cancer
#6
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/29303360/flaxseed-lignans-enhance-the-cytotoxicity-of-chemotherapeutic-agents-against-breast-cancer-cell-lines-mda-mb-231-and-skbr3
#7
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...
February 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29227654/synergistic-chemopreventive-and-therapeutic-effects-of-co-drug-ua-met-implication-in-tumor-metastasis
#8
Guirong Zheng, Zhichun Shen, Aixiao Xu, Kai Jiang, Pengyu Wu, Xiang Yang, Xian Chen, Jingwei Shao
The anticancer properties of ursolic acid (UA) and metformin (Met) have been well demonstrated. However, whether these compounds can act synergistically to prevent and treat cancer is not known. We present in this study, the synergism between UA and Met, and that of a new codrug made of UA and Met (UA-Met) against several cancer cell lines. The combination of high concentration of UA (25, 50, 75, 100 μM) and Met (5, 10, 20, 40 mM) resulted in synergetic cytotoxicity on MDA-MB-231 and MCF-7 cells (CI < 0...
December 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29211738/metformin-inhibits-the-development-and-promotes-the-resensitization-of-treatment-resistant-breast-cancer
#9
Gerald Davies, Liubov Lobanova, Wojciech Dawicki, Gary Groot, John R Gordon, Matthew Bowen, Troy Harkness, Terra Arnason
Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors...
2017: PloS One
https://www.readbyqxmd.com/read/29200002/metformin-and-melatonin-inhibit-dmba-induced-mammary-tumorigenesis-in-rats-fed-a-high-fat-diet
#10
Bianka Bojková, Karol Kajo, Terézia Kisková, Peter Kubatka, Pavol Žúbor, Peter Solár, Martin Péč, Marián Adamkov
The data from in-vitro and in-vivo studies show that both peroral antidiabetic metformin (MF) and pineal hormone melatonin (MT) inhibit the growth of many cancers, including breast cancer. However, most in-vivo studies used standard-type diet with low fat content. Therefore, in this study, we evaluated the chemopreventive effect of MF and MT in an in-vivo model of breast cancer in rats on a high-fat diet (10% of total fat). Mammary carcinogenesis was induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats...
December 1, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29137418/a-randomized-phase-ii-study-of-aromatase-inhibitors-plus-metformin-in-pre-treated-postmenopausal-patients-with-hormone-receptor-positive-metastatic-breast-cancer
#11
Yannan Zhao, Chengcheng Gong, Zhonghua Wang, Jian Zhang, Leiping Wang, Sheng Zhang, Jun Cao, Zhonghua Tao, Ting Li, Biyun Wang, Xichun Hu
Background: Everolimus significantly improves progression-free survival (PFS) and has been approved to use in aromatase inhibitor pretreated patients with hormone receptor positive advanced breast cancer. Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors. Methods: 60 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer were randomly assigned 1:1 to aromatase inhibitor (exemestane 25mg/d or letrozole 2...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111858/women-s-health-endocrine-update
#12
Ekta Kapoor, Stephanie Faubion, Stephanie Hines, Cynthia A Stuenkel
The clinical update serves as a brief review of recently published, high-impact, and potentially practice changing journal articles summarized for our readers. Topics include menopause, sexual dysfunction, breast health, contraception, osteoporosis, and cardiovascular disease. In this clinical update, we selected four recent high-impact publications related to endocrine issues in women. We have chosen to highlight research on subclinical hypothyroidism during pregnancy and adverse pregnancy outcomes, including cognitive outcomes in offspring; the progression of metabolic syndrome severity during the menopausal transition; and the association of diabetes and metformin use with cancer risk and mortality...
November 7, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/29026839/missing-the-benefit-of-metformin-in-acute-myeloid-leukemia-a-problem-of-contrast
#13
Alice C Ceacareanu, George K Nimako, Zachary A P Wintrob
OBJECTIVE: To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. METHODS: Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR])...
July 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/29022647/use-of-metformin-is-associated-with-lower-incidence-of-cancer-in-patients-with-type-2-diabetes
#14
Alicja Muszyńska-Ogłaza, Grażyna Zarzycka-Lindner, Henryka Olejniczak, Mirosława Polaszewska-Muszyńska, Roman Junik
INTRODUCTION: The objective of the study was to assess the influence of metformin on the prevalence of cancer and risk factors for the development of cancer, in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 1063 patients, treated between October 2012 and March 2013 in the Diabetes and Endocrinology Centre in Bydgoszcz, were enrolled in the study. Only patients who were first diagnosed with diabetes and consecutively with cancer were included in the analysis...
October 12, 2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28988825/pgc-1%C3%AE-promotes-breast-cancer-metastasis-and-confers-bioenergetic-flexibility-against-metabolic-drugs
#15
Sylvia Andrzejewski, Eva Klimcakova, Radia M Johnson, Sébastien Tabariès, Matthew G Annis, Shawn McGuirk, Jason J Northey, Valérie Chénard, Urshila Sriram, David J Papadopoli, Peter M Siegel, Julie St-Pierre
Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1α compared with those that metastasize to the liver. PGC-1α promotes breast cancer cell migration and invasion in vitro and augments lung metastasis in vivo. Pro-metastatic capabilities of PGC-1α are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides...
November 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28978007/differences-in-risk-factors-of-malignancy-between-men-and-women-with-type-2-diabetes-a-retrospective-case-control-study
#16
Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak
BACKGROUND: The aim of this multicenter, retrospective, case-control study was to identify differences in risk factors of malignancy between men and women with type 2 diabetes. RESULTS: Among women the most prevalent malignancies were: breast and uterine cancers (35.6% and 14.4% respectively), while among men there were: colorectal and prostate cancers (24.5% and 13.3% respectively). In both gender metformin use was associated with lower cancer risk. Obesity and insulin treatment in dose-dependent and time-varying manner were associated with significantly increased risk of malignancy in females...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28967197/sugar-coated-nanobullet-growth-inhibition-of-cancer-cells-induced-by-metformin-loaded-glyconanoparticles
#17
Ruo-Can Qian, Jian Lv, Hao-Wen Li, Yi-Tao Long
Metformin, a widely used drug for treating type-2 diabetes, has now been discovered to reduce cancer cell proliferation. However, further efforts are needed to design effective metformin delivery vehicles, instead of bare metformin. Herein we report a highly efficient transport nanostructure based on core-shell glyconanoparticles (GNPs), with gold as the core and dextran as the shell interspersed with metformin molecules. The dextran shell facilitates the entry of GNPs into living cells, which allows the subsequent release of metformin...
October 1, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28947975/phenformin-inhibits-growth-and-epithelial-mesenchymal-transition-of-erbb2-overexpressing-breast-cancer-cells-through-targeting-the-igf1r-pathway
#18
Zhiying Guo, Ming Zhao, Erin W Howard, Qingxia Zhao, Amanda B Parris, Zhikun Ma, Xiaohe Yang
Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation. Although the anti-cancer properties of metformin have been well-studied, reports on a more bioavailable/potent biguanide, phenformin, remain sparse. Phenformin exerts similar functional activity to metformin and has been reported to impede mammary carcinogenesis in rats. Since the effects of phenformin on specific breast cancer subtypes have not been fully explored, we used ErbB2-overexpressing breast cancer cell and animal models to test the anti-cancer potential of phenformin...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935814/diabetes-treatments-and-risks-of-adverse-breast-cancer-outcomes-among-early-stage-breast-cancer-patients-a-seer-medicare-analysis
#19
Lu Chen, Jessica Chubak, Denise M Boudreau, William E Barlow, Noel S Weiss, Christopher I Li
The widely prescribed diabetes medicine metformin has been reported to lower the risk of incident breast cancer, but it is unclear whether it affects malignant progression after diagnosis. In this study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28928832/downregulation-of-rab27a-contributes-to-metformin-induced-suppression-of-breast-cancer-stem-cells
#20
Feixue Feng, Jianping Zhang, Xiaoxuan Fan, Fang Yuan, Yinghao Jiang, Ruihua Lv, Yanxia Ma
Cancer stem cells (CSCs) are associated with tumor initiation, therapeutic resistance, relapse and metastasis. However, the underlying mechanisms CSCs use to preserve stemness are not yet fully understood. The present study demonstrated that the expression of RAB27A, member RAS oncogene family (Rab27a), which was reported to promote tumor progression by upregulating exocytosis of extracellular vesicles, was higher in mammosphere cells than in adherent MDA-MB-231 breast cancer cells. Downregulation of Rab27A inhibited mammosphere formation by decreasing the proportion of CD44+CD24-/low cells of the MDA-MB-231 cell line...
September 2017: Oncology Letters
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