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Metformin breast cancer

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https://www.readbyqxmd.com/read/29227654/synergistic-chemopreventive-and-therapeutic-effects-of-co-drug-ua-met-implication-in-tumor-metastasis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#14
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
October 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918830/metformin-has-positive-therapeutic-effects-in-colon-cancer-and-lung-cancer
#15
DeAnna Henderson, Danielle Frieson, Jeffrey Zuber, Solomon S Solomon
BACKGROUND: Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180)...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28856166/ketoacidosis-with-canagliflozin-prescribed-for-phosphoinositide-3-kinase-inhibitor-induced-hyperglycemia-a-case-report
#16
Christopher Bowman, Vandana Abramson, Melissa Wellons
Context. Many phosphoinositide-3-kinase (PI3K) inhibitors are under trial for cancer treatment. We present a patient taking taselisib who developed ketoacidosis within 1 week of starting canagliflozin. Case Description. A 69-year-old female patient with no previous history of diabetes mellitus was enrolled in a clinical trial for taselisib therapy in stage IV breast cancer. Hyperglycemia treatment with metformin was insufficient and not tolerated. The addition of canagliflozin daily resulted in ketoacidosis and hospitalization within 1 week...
July 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28840596/risk-of-cause-specific-death-in-individuals-with-cancer-modifying-role-diabetes-statins-and-metformin
#17
Jari Haukka, Leo Niskanen, Anssi Auvinen
Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all-cause and cause-specific mortality dynamics in relation to baseline DM, statin use and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow-up and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage and calendar period...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28819383/metformin-inhibits-tumorigenesis-and-tumor-growth-of-breast-cancer-cells-by-upregulating-mir-200c-but-downregulating-akt2-expression
#18
Jiali Zhang, Gefei Li, Yuan Chen, Lei Fang, Chen Guan, Fumao Bai, Mengni Ma, Jianxin Lyu, Qing H Meng
Background: Metformin has been reported to inhibit the growth of various types of cancers, including breast cancer. Yet the mechanisms underlying the anticancer effects of metformin are not fully understood. Growing evidence suggests that metformin's anticancer effects are mediated at least in part by modulating microRNAs, including miR-200c, which has a tumor suppressive role in breast cancer. We hypothesized that miR-200c has a role in the antitumorigenic effects of metformin on breast cancer cells. Methods: To delineate the role of miR-200c in the effects of metformin on breast cancer, plasmids containing pre-miR-200c or miR-200c inhibitor were transfected into breast cancer cell lines...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28802138/inhibition-of-bioenergetic-metabolism-by-the-combination-of-metformin-and-2-deoxyglucose-highly-decreases-viability-of-feline-mammary-carcinoma-cells
#19
María Florencia Arbe, Chiara Fondello, Lucrecia Agnetti, Gabriel Martín Álvarez, Matías Nicolás Tellado, Gerardo Claudio Glikin, Liliana María Elena Finocchiaro, Marcela Solange Villaverde
Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3+) and Ki67<5%) and AlRATN (HER2 (-) and Ki67>15%)...
August 3, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28782285/metformin-enhances-doxorubicin-sensitivity-via-inhibition-of-doxorubicin-efflux-in-p-gp-overexpressing-mcf-7-cells
#20
Vahid Shafiei-Irannejad, Nasser Samadi, Bahman Yousefi, Roya Salehi, Kobra Velaei, Nosratollah Zarghami
Resistance against chemotherapy is still a major problem in successful cancer treatment in the clinic. Therefore, identifying new compounds with lower side effects and higher efficacy is an important approach to overcome multidrug resistance (MDR). Here, we investigated the activity and possible mechanism of the antidiabetic drug, metformin, in human doxorubicin (DOX) resistant breast cancer (MCF-7/DOX) cells. The effect of metformin on the cytotoxicity of DOX was evaluated by MTT assay. The P-gp mRNA/protein expression levels following treatment with metformin was determined using real time polymerase chain reaction (RT-PCR) and western blot analysis, respectively...
August 6, 2017: Chemical Biology & Drug Design
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