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Metformin and breast cancer

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https://www.readbyqxmd.com/read/28928832/downregulation-of-rab27a-contributes-to-metformin-induced-suppression-of-breast-cancer-stem-cells
#1
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
#2
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...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918830/metformin-has-positive-therapeutic-effects-in-colon-cancer-and-lung-cancer
#3
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
#4
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
#5
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...
August 25, 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28754674/adipose-progenitor-cell-secretion-of-gm-csf-and-mmp9-promotes-a-stromal-and-immunological-microenvironment-that-supports-breast-cancer-progression
#9
Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Cristina Rabascio, Giovanna Talarico, Stefania Orecchioni, Andrea Manconi, Francesco Bertolini
A cell population with progenitor-like phenotype (CD45-CD34+) resident in human white adipose tissue (WAT) is known to promote the progression of local and metastatic breast cancer and angiogenesis. However, the molecular mechanisms of the interaction have not been elucidated. In this study, we identified two proteins that were significantly up-regulated in WAT-derived progenitors after co-culture with breast cancer: granulocyte-macrophage colony-stimulating factor (GM-CSF) and matrix metallopeptidase 9 (MMP9)...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#10
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28742810/effect-of-calcium-electroporation-in-combination-with-metformin-in-vivo-and-correlation-between-viability-and-intracellular-atp-level-after-calcium-electroporation-in-vitro
#11
Stine Krog Frandsen, Julie Gehl
BACKGROUND: Calcium electroporation is a new experimental anti-cancer treatment where calcium is internalized into cells by application of short, high voltage pulses. Calcium electroporation has been shown to induce tumor necrosis associated with ATP depletion while the effect on normal fibroblasts was limited when investigated in a 3D in vitro spheroid model. We aimed to investigate the effect of calcium electroporation in combination with metformin, a drug that affects intracellular ATP level...
2017: PloS One
https://www.readbyqxmd.com/read/28698800/metformin-induced-ablation-of-microrna-21-5p-releases-sestrin-1-and-cab39l-antitumoral-activities
#12
Claudio Pulito, Federica Mori, Andrea Sacconi, Frauke Goeman, Maria Ferraiuolo, Patrizia Pasanisi, Carlo Campagnoli, Franco Berrino, Maurizio Fanciulli, Rebecca J Ford, Massimo Levrero, Natalia Pediconi, Ludovica Ciuffreda, Michele Milella, Gregory R Steinberg, Mario Cioce, Paola Muti, Sabrina Strano, Giovanni Blandino
Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28698536/metformin-use-associated-with-lower-risk-of-cancer-in-patients-with-diabetes-mellitus-type-2
#13
Jasna Kusturica, Aida Kulo Ćesić, Edis Gušić, Sanita Maleškić, Maida Rakanović-Todić, Damir Šečić
Aim In order to increase the database related to the antineoplastic potential of metformin, association between the use of metformin and risk of cancer occurence in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this cross-sectional study, medical records of patients with DM2 were reviewed for cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine consumption, glucose and HbA1c levels, duration of DM2, medication used in the treatment of DM2 and cancer occurence were collected and analyzed...
August 1, 2017: Medicinski Glasnik
https://www.readbyqxmd.com/read/28678551/nano-encapsulated-metformin-curcumin-in-plga-peg-inhibits-synergistically-growth-and-htert-gene-expression-in-human-breast-cancer-cells
#14
Raana Farajzadeh, Younes Pilehvar-Soltanahmadi, Mehdi Dadashpour, Shahrzad Javidfar, Javid Lotfi-Attari, Hadi Sadeghzadeh, Vahid Shafiei-Irannejad, Nosratollah Zarghami
The study was aimed at investigating the synergistic inhibitory effect of unique combinational regimen of nanocapsulated Metformin (Met) and Curcumin (Cur) against T47D breast cancer cells. For this purpose, Met and Cur were co-encapsulated in PEGylated PLGA nanoparticles (NPs) and evaluated for their therapeutic efficacy. The morphology and dynamic light scattering (DLS) analyses were carried out to optimize the nanoformulations. Drug release study was performed using dialysis method and then the cytotoxic and inhibitory effect of individual and combined drugs on expression level of hTERT in T47D breast cell line were evaluated using MTT assay and qPCR, respectively...
July 5, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28675758/metformin-suppresses-proliferation-and-viability-of-rat-pheochromocytoma-cells
#15
Min Li, Xiuli Jiang, Tingwei Su, Lei Jiang, Weiwei Zhou, Weiqing Wang
BACKGROUND Previous studies have clearly demonstrated that metformin inhibits cell proliferation and cell growth in many types of human cancers. Increased survival rates in patients with breast and lung cancer receiving metformin have also been observed. However, the effect of metformin on pheochromocytoma cells remains unexplored. MATERIAL AND METHODS Rat pheochromocytoma cells (PC12 cells) were cultured and treated with metformin or vehicle control. Cell proliferation, cell-cycle, apoptosis, genes expression, and the signaling pathways involved were analyzed in PC12 cells...
July 4, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28537928/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...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#17
Safar Kheder, Karen Sisley, Sirwan Hadad, Sabapathy P Balasubramanian
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28521859/-evaluation-of-primary-adherence-to-medications-in-patients-with-chronic-conditions-a-retrospective-cohort-study
#18
Francisco Emiliano Peper, Santiago Esteban, Sergio Adrian Terrasa
OBJECTIVES: To assess the proportion of members of a private health insurance at the Hospital Italiano de Buenos Aires with primary adherence to, 1) bisphosphonates for secondary prevention of osteoporotic fractures, 2) insulin and metformin in type 2 diabetes, and 3) tamoxifen in the context of treatment of breast cancer. DESIGN: Retrospective cohort study to determine the proportion of primary treatment adherence during 2012 and 2013. SITE: Hospital Italiano de Buenos Aires, Argentina...
May 15, 2017: Atencion Primaria
https://www.readbyqxmd.com/read/28496098/combined-treatment-with-metformin-and-2-deoxy-glucose-induces-detachment-of-viable-mda-mb-231-breast-cancer-cells-in-vitro
#19
Maruša Bizjak, Petra Malavašič, Klemen Dolinar, Jelka Pohar, Sergej Pirkmajer, Mojca Pavlin
Triple naegative breast cancer has an increased rate of distant metastasis and consequently poor prognosis. To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize in vivo, the viability of floating cancer cells in vitro is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28491145/combination-of-metformin-and-curcumin-targets-breast-cancer-in-mice-by-angiogenesis-inhibition-immune-system-modulation-and-induction-of-p53-independent-apoptosis
#20
Rabah Rashad Falah, Wamidh H Talib, Seba Jamal Shbailat
BACKGROUND: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. MATERIALS AND METHODS: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells...
April 2017: Therapeutic Advances in Medical Oncology
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