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Metformin and breast cancer

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https://www.readbyqxmd.com/read/29780974/metformin-targets-glucose-metabolism-in-triple-negative-breast-cancer
#1
R S Wahdan-Alaswad, S M Edgerton, H S Salem, A D Thor
Metformin is the most widely administered anti-diabetic agent worldwide. In patients receiving metformin for metabolic syndrome or diabetes, it reduces the incidence and improves the survival of breast cancer (BC) patients. We have previously shown that metformin is particularly potent against triple negative breast cancer (TNBC), with a reduction of proliferation, oncogenicity and motility, inhibition of pro-oncogenic signaling pathways and induction of apoptosis. These BCs are well recognized to be highly dependent on glucose/glucosamine (metabolized through anaerobic glycolysis) and lipids, which are metabolized for the production of energy and cellular building blocks to sustain a high rate of proliferation...
2018: Journal of Oncology Translational Research
https://www.readbyqxmd.com/read/29770821/a-size-shrinkable-nanoparticle-based-combined-anti-tumor-and-anti-inflammatory-strategy-for-enhanced-cancer-therapy
#2
Zhengze Lu, Yang Long, Xingli Cun, Xuhui Wang, Jianping Li, Ling Mei, Yiliang Yang, Man Li, Zhirong Zhang, Qin He
Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy...
May 17, 2018: Nanoscale
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#3
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29693804/synergistic-growth-inhibitory-effects-of-chrysin-and-metformin-combination-on-breast-cancer-cells-through-htert-and-cyclin-d1-suppression
#4
Sara Rasouli, Nosratollah Zarghami
Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment, the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancer cells were investigated. Materials and Methods: After treatment of T47D cells with Metformin, Chrysin and the two drugs in combination, toxicity to cancer cells was evaluated by MTT assay. Real time PCR was then used to determine the expression levels of hTERT and cyclin D1 genes. Results: The MTT test findings showed that the combination of metformin and chrysin had high synergistic effects in killing cancer cells...
April 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29671072/reversion-of-multidrug-resistance-by-co-encapsulation-of-doxorubicin-and-metformin-in-poly-lactide-co-glycolide-d-%C3%AE-tocopheryl-polyethylene-glycol-1000-succinate-nanoparticles
#5
Vahid Shafiei-Irannejad, Nasser Samadi, Roya Salehi, Bahman Yousefi, Mahdi Rahimi, Abolfazl Akbarzadeh, Nosratollah Zarghami
PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages...
April 18, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29663879/anti-cancer-effects-of-metformin-recent-evidences-for-its-role-in-prevention-and-treatment-of-cancer
#6
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Warda Kamal, Mohammad A Kamal
Metformin is widely used for the management of type 2 diabetes mellitus (T2DM). Recently growing evidence has shown its anti-cancer effects. The results are mainly obtained from observational studies and thus, little information is available concerning the mechanisms of action. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays an important role in the mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects, whereas the decrease in glucose level, hyperinsulinemia, and Insulin-like growth factor 1 (IGF-1) level was considered its indirect effects...
April 16, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29624460/novel-quinoxaline-2-carbonitrile-1-4-dioxide-derivatives-suppress-hif1%C3%AE-activity-and-circumvent-mdr-in-cancer-cells
#7
Alexander M Scherbakov, Alexander M Borunov, Galina I Buravchenko, Olga E Andreeva, Igor A Kudryavtsev, Lyubov G Dezhenkova, Andrey E Shchekotikhin
A series of 3-aryl/hetarylquinoxaline-2-carbonitrile-1,4-dioxides was synthesized and evaluated against breast cancer cell lines in normoxia and hypoxia. Selected compounds in this series demonstrated better cytotoxicity and comparable hypoxia selectivity than tirapazamine. In contrast to Dox, quinoxaline-1,4-dioxides showed potent cytotoxicity against different MDR cells. Compound 2g inhibits of cancer cell growth through p53-independent mechanisms. Our results showed that compound 2g sensitized MCF-7 cells to metformin in hypoxia...
April 6, 2018: Cancer Investigation
https://www.readbyqxmd.com/read/29618465/association-of-metformin-with-breast-cancer-incidence-and-mortality-in-patients-with-type-2-diabetes-a-grade-assessed-systematic-review-and-meta-analysis
#8
Grace H Tang, Meloja Satkunam, Gregory R Pond, Gregory R Steinberg, Giovanni Blandino, Holger J Schünemann, Paola Muti
BACKGROUND: Preclinical data suggests that metformin may reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence of breast cancer and all-cause mortality in patients with type 2 diabetes (T2D). METHODS: A literature search was performed on Medline, EMBASE, and the Cochrane library from inception to November 2016...
April 4, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29617321/exosome-mediated-transfer-of-cancer-cell-resistance-to-antiestrogen-drugs
#9
Svetlana E Semina, Alexander M Scherbakov, Anna A Vnukova, Dmitry V Bagrov, Evgeniy G Evtushenko, Vera M Safronova, Daria A Golovina, Ludmila N Lyubchenko, Margarita V Gudkova, Mikhail A Krasil'nikov
Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery...
April 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29610032/personalized-prevention-in-high-risk-individuals-managing-hormones-and-beyond
#10
D Gareth Evans, Sacha J Howell, Anthony Howell
Increasing numbers of women are being identified at 'high-risk' of breast cancer, defined by The National Institute of Health and Care Excellence (NICE) as a 10-year risk of ≥8%. Classically women have been so identified through family history based risk algorithms or genetic testing of high-risk genes. Recent research has shown that assessment of mammographic density and single nucleotide polymorphisms (SNPs), when combined with established risk factors, trebles the number of women reaching the high risk threshold...
March 30, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29552226/the-co-treatment-of-metformin-with-flavone-synergistically-induces-apoptosis-through-inhibition-of-pi3k-akt-pathway-in-breast-cancer-cells
#11
Zhaodi Zheng, Wenzhen Zhu, Bingwu Yang, Rongfei Chai, Tingting Liu, Fenglin Li, Guanghui Ren, Shuhua Ji, Shan Liu, Guorong Li
Metformin, a widely used antidiabetic drug, exhibits anticancer effects which are mediated by the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) signaling pathway. However, its use in anticancer therapy combined with other natural products remains unclear. Flavone as the core structure of flavonoids has been demonstrated to induce cell apoptosis without causing serious side effect. Murine double minute X (MDMX) inhibits tumor suppressor gene p53 whose function is associated with the PI3K/AKT pathway...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29550639/effect-of-metformin-on-estrogen-and-progesterone-receptor-positive-mcf-7-and-triple-negative-mda-mb-231-breast-cancer-cells
#12
Inês Amaral, Cláudia Silva, Ana Correia-Branco, Fátima Martel
This work aimed to investigate the effect of metformin on cellular glucose uptake and metabolism by breast cancer cells, as a mechanism contributing to its anticancer properties. Estrogen and progesterone receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines were used as in vitro models of breast cancer. Short-term (26 min) exposure of MCF-7 and MDA-MB-231 cells to metformin inhibited uptake of3 H-deoxy-D-glucose (3 H-DG). In contrast, long-term (24 h) exposure to metformin (5 μM-1 mM) concentration-dependently increased3 H-DG uptake in both cell lines...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29545399/specificity-protein-transcription-factors-and-cancer-opportunities-for-drug-development
#13
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29541397/a-usable-model-of-decathlon-winner-cancer-cells-in-triple-negative-breast-cancer-survival-of-resistant-cancer-cells-in-quiescence
#14
Balraj Singh, Vanessa N Sarli, Laura J Washburn, Milan R Raythatha, Anthony Lucci
We previously described a strategy for selecting highly adaptable rare triple-negative breast cancer (TNBC) cells based on their ability to survive a severe and prolonged metabolic challenge, e.g., a lack of glutamine. We hypothesized that metabolically adaptable (MA) cancer cells selected from the SUM149 cell line in this manner have the capacity to survive a variety of challenges that postulated "decathlon winner" cancer cells must survive to succeed in metastasis. These MA cells were resistant to glutaminase inhibitor CB-839, as predicted from their ability to proliferate without exogenous glutamine...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29540614/obesity-promotes-resistance-to-anti-vegf-therapy-in-breast-cancer-by-up-regulating-il-6-and-potentially-fgf-2
#15
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29515760/molecular-characterization-of-breast-cancer-cell-response-to-metabolic-drugs
#16
Lucía Trilla-Fuertes, Angelo Gámez-Pozo, Jorge M Arevalillo, Mariana Díaz-Almirón, Guillermo Prado-Vázquez, Andrea Zapater-Moros, Hilario Navarro, Rosa Aras-López, Irene Dapía, Rocío López-Vacas, Paolo Nanni, Sara Llorente-Armijo, Pedro Arias, Alberto M Borobia, Paloma Maín, Jaime Feliú, Enrique Espinosa, Juan Ángel Fresno Vara
Metabolic reprogramming is a hallmark of cancer. It has been described that breast cancer subtypes present metabolism differences and this fact enables the possibility of using metabolic inhibitors as targeted drugs in specific scenarios. In this study, breast cancer cell lines were treated with metformin and rapamycin, showing a heterogeneous response to treatment and leading to cell cycle disruption. The genetic causes and molecular effects of this differential response were characterized by means of SNP genotyping and mass spectrometry-based proteomics...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29500444/metformin-induced-caveolin-1-expression-promotes-t-dm1-drug-efficacy-in-breast-cancer-cells
#17
Yuan-Chiang Chung, Ching-Ming Chang, Wan-Chen Wei, Ting-Wei Chang, King-Jen Chang, Wei-Ting Chao
Trastuzumab emtansine (T-DM1) is an antibody drug conjugate (ADC) that was recently approved for the treatment of HER-2-positive metastatic breast cancer. The drug sensitivity of ADCs depends mainly on the internalization efficiency of the drug. Caveolin-1 was shown to promote T-DM1 internalization and enhance drug sensitivity. Whether caveolin-1 can be overexpressed to improve T-DM1 efficacy is interesting and has the potential for clinical application. In this study, diabetes drug metformin was investigated in terms of induction of caveolin-1 expression for increased efficacy of subsequent T-DM1 application...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29500390/development-of-an-injectable-slow-release-metformin-formulation-and-evaluation-of-its-potential-antitumor-effects
#18
Sara Baldassari, Agnese Solari, Guendalina Zuccari, Giuliana Drava, Sara Pastorino, Carmen Fucile, Valeria Marini, Antonio Daga, Alessandra Pattarozzi, Alessandra Ratto, Angelo Ferrari, Francesca Mattioli, Federica Barbieri, Gabriele Caviglioli, Tullio Florio
Metformin is an antidiabetic drug which possesses antiproliferative activity in cancer cells when administered at high doses, due to its unfavorable pharmacokinetics. The aim of this work was to develop a pharmacological tool for the release of metformin in proximity of the tumor, allowing high local concentrations, and to demonstrate the in vivo antitumor efficacy after a prolonged metformin exposition. A 1.2% w/w metformin thermoresponsive parenteral formulation based on poloxamers P407 and P124, injectable at room temperature and undergoing a sol-gel transition at body temperature, has been developed and optimized for rheological, thermal and release control properties; the formulation is easily scalable, and proved to be stable during a 1-month storage at 5 °C...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29486734/the-association-of-diabetes-mellitus-and-insulin-treatment-with-expression-of-insulin-related-proteins-in-breast-tumors
#19
Heleen K Bronsveld, Marie L De Bruin, Jelle Wesseling, Joyce Sanders, Ingrid Hofland, Vibeke Jensen, Marloes T Bazelier, Bas Ter Braak, Anthonius de Boer, Peter Vestergaard, Marjanka K Schmidt
BACKGROUND: The insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer. We aimed to evaluate the expression of hormone and insulin-related proteins within or related to the PI3K and MAPK pathway in breast tumors of women with or without diabetes mellitus, treated with or without insulin (analogues). METHODS: Immunohistochemistry was performed on tumor tissue of 312 women with invasive breast cancer, with or without pre-existing diabetes mellitus, diagnosed in 2000-2010, who were randomly selected from a Danish breast cancer cohort...
February 27, 2018: BMC Cancer
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
#20
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
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