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Cancer AND Metformin AND Mitochondria

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https://www.readbyqxmd.com/read/27746051/metformin-targets-central-carbon-metabolism-and-reveals-mitochondrial-requirements-in-human-cancers
#1
Xiaojing Liu, Iris L Romero, Lacey M Litchfield, Ernst Lengyel, Jason W Locasale
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors...
October 12, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27216187/mitochondria-targeted-analogues-of-metformin-exhibit-enhanced-antiproliferative-and-radiosensitizing-effects-in-pancreatic-cancer-cells
#2
Gang Cheng, Jacek Zielonka, Olivier Ouari, Marcos Lopez, Donna McAllister, Kathleen Boyle, Christy S Barrios, James J Weber, Bryon D Johnson, Micael Hardy, Michael B Dwinell, Balaraman Kalyanaraman
Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+))...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27168791/metformin-induces-apoptosis-via-a-mitochondria-mediated-pathway-in-human-breast-cancer-cells-in-vitro
#3
Zhen-Yuan Gao, Zhe Liu, Ming-Hong Bi, Jing-Jing Zhang, Zheng-Quan Han, Xiao Han, Hong-Ya Wang, Guo-Ping Sun, Hao Liu
Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435...
May 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27101310/high-glucose-induces-down-regulated-grim-19-expression-to-activate-stat3-signaling-and-promote-cell-proliferation-in-cell-culture
#4
Yong-Guang Li, Bei-Bei Han, Feng Li, Jian-Wu Yu, Zhi-Feng Dong, Geng-Ming Niu, Yan-Wei Qing, Jing-Bo Li, Meng Wei, Wei Zhu
Recent studies indicated that Gene Associated with Retinoid-IFN-Induced Mortality 19 (GRIM-19), a newly discovered mitochondria-related protein, can regulate mitochondrial function and modulate cell viability possibly via interacting with STAT3 signal. In the present study we sought to test: 1) whether GRIM-19 is involved in high glucose (HG) induced altered cell metabolism in both cancer and cardiac cells, 2) whether GRIM-19/STAT3 signaling pathway plays a role in HG induced biological effects, especially whether AMPK activity could be involved...
2016: PloS One
https://www.readbyqxmd.com/read/27082123/metformin-induces-apoptosis-by-microrna-26a-mediated-downregulation-of-myeloid-cell-leukaemia-1-in-human-oral-cancer-cells
#5
Fang Wang, Jincheng Xu, Hao Liu, Zhe Liu, Fei Xia
In recent years, population-based studies and retrospective analyses of clinical studies have shown that metformin treatment is associated with reduced cancer incidence and a decrease in cancer‑associated mortality. However, its mechanism of action remains to be fully understood. The present study demonstrates the effects of metformin on KB human oral cancer cells and explores the role of myeloid cell leukaemia‑1 (Mcl‑1) in metformin‑induced mitochondria‑dependent cellular apoptosis. It was demonstrated that metformin exposure caused significant suppression of KB cell proliferation and induced cell death...
June 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27080907/unique-fractal-evaluation-and-therapeutic-implications-of-mitochondrial-morphology-in-malignant-mesothelioma
#6
Frances E Lennon, Gianguido C Cianci, Rajani Kanteti, Jacob J Riehm, Qudsia Arif, Valeriy A Poroyko, Eitan Lupovitch, Wickii Vigneswaran, Aliya Husain, Phetcharat Chen, James K Liao, Martin Sattler, Hedy L Kindler, Ravi Salgia
Malignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism. MM cell lines display a spectrum of altered mitochondrial morphologies and function compared to control mesothelial cells. Fractal dimension and lacunarity measurements are a sensitive and objective method to quantify mitochondrial morphology and most importantly are a promising predictor of response to mitochondrial inhibition...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26625127/metformin-antagonizes-cancer-cell-proliferation-by-suppressing-mitochondrial-dependent-biosynthesis
#7
Takla Griss, Emma E Vincent, Robert Egnatchik, Jocelyn Chen, Eric H Ma, Brandon Faubert, Benoit Viollet, Ralph J DeBerardinis, Russell G Jones
Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC). However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK) and LKB1 are not required for the antiproliferative effects of metformin...
December 2015: PLoS Biology
https://www.readbyqxmd.com/read/26622674/metformin-inhibits-growth-of-lung-adenocarcinoma-cells-by-inducing-apoptosis-via-the-mitochondria-mediated-pathway
#8
Junling Wang, Qiuling Gao, Decui Wang, Zhiqiang Wang, Chun Hu
Metformin is commonly used to treat type II diabetes, although it may also reduce the risk of cancer and improve the associated prognosis. However, its mode of action in cancer remains unclear. The present study evaluated the effects of metformin on lung adenocarcinoma A549 cells and identified molecular mechanisms of metformin activity. The A549 cells were treated with metformin at different concentrations and cell viability was assayed by using an MTT assay. The cell cycle and the apoptosis rate were assayed by flow cytometry...
September 2015: Oncology Letters
https://www.readbyqxmd.com/read/26605341/breast-cancer-metabolism-and-mitochondrial-activity-the-possibility-of-chemoprevention-with-metformin
#9
REVIEW
Massimiliano Cazzaniga, Bernardo Bonanni
Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation...
2015: BioMed Research International
https://www.readbyqxmd.com/read/26503999/relationship-between-metabolic-reprogramming-and-mitochondrial-activity-in-cancer-cells-understanding-the-anticancer-effect-of-metformin-and-its-clinical-implications
#10
REVIEW
Massimiliano Cazzaniga, Bernardo Bonanni
Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. This adaptation comprises of some important bioenergetic changes that, in contrary to conventional and outdated concepts, require an unchanged mitochondrial activity for their efficacy. This review highlights the characteristics of metabolic reprogramming, the role of mitochondrial activity in this particular setting, and the therapeutic possibility of targeting pathways of energy metabolism in cancer cells, with particular emphasis on metformin efficacy and its relationship with mitochondria metabolism...
November 2015: Anticancer Research
https://www.readbyqxmd.com/read/26288997/characterization-and-evaluation-of-metformin-loaded-solid-lipid-nanoparticles-for-celluar-and-mitochondrial-uptake
#11
Qiang Xu, Tao Zhu, Chaoli Yi, Qi Shen
Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin-SLNs were prepared using an emulsification and low-temperature solidification method...
2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/26277279/metformin-and-cancer-between-the-bioenergetic-disturbances-and-the-antifolate-activity
#12
REVIEW
J A Jara, R López-Muñoz
For decades, metformin has been the first-line drug for the treatment of type II diabetes mellitus, and it thus is the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. In this review, we summarize the current molecular evidence in an effort to elucidate metformin's mode of action against cancer cells...
November 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/26258801/characterization-and-evaluation-of-metformin-loaded-solid-lipid-nanoparticles-for-celluar-and-mitochondrial-uptake
#13
Qiang Xu, Tao Zhu, Chaoli Yi, Qi Shen
Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin-SLNs were prepared using an emulsification and low-temperature solidification method...
August 10, 2015: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/26215782/metformin-and-prostate-cancer-stem-cells-a-novel-therapeutic-target
#14
REVIEW
M J Mayer, L H Klotz, V Venkateswaran
Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence...
December 2015: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/26148596/sensitization-to-oxaliplatin-in-hct116-and-ht29-cell-lines-by-metformin-and-ribavirin-and-differences-in-response-to-mitochondrial-glutaminase-inhibition
#15
Silvina M Richard, Veronica L Martinez Marignac
AIM OF STUDY: In the present study, we evaluated the effect of ribavirin and metformin on the sensitivity of oxaliplatin and 5-fluorouracil (5-FU) on colon cancer. MATERIALS AND METHODS: Cell viability of two commercially available colon cancer cell lines (HT29 and HCT116) were analyzed by sulforhodamine B (SRB) assay. RESULTS: A clinically achievable and nontoxic concentration of ribavirin and metformin showed a significant synergistic effect on oxaliplatin in HT29 and HCT116 cell lines...
April 2015: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/26133123/energy-metabolism-determines-the-sensitivity-of-human-hepatocellular-carcinoma-cells-to-mitochondrial-inhibitors-and-biguanide-drugs
#16
Chia-Chi Hsu, Ling-Chia Wu, Cheng-Yuan Hsia, Pen-Hui Yin, Chin-Wen Chi, Tien-Shun Yeh, Hsin-Chen Lee
Human hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide particularly in Asia. Deregulation of cellular energetics was recently included as one of the cancer hallmarks. Compounds that target the mitochondria in cancer cells were proposed to have therapeutic potential. Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients...
September 2015: Oncology Reports
https://www.readbyqxmd.com/read/26041263/how-do-changes-in-the-mtdna-and-mitochondrial-dysfunction-influence-cancer-and-cancer-therapy-challenges-opportunities-and-models
#17
REVIEW
M W van Gisbergen, A M Voets, M H W Starmans, I F M de Coo, R Yadak, R F Hoffmann, P C Boutros, H J M Smeets, L Dubois, P Lambin
Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction...
April 2015: Mutation Research. Reviews in Mutation Research
https://www.readbyqxmd.com/read/26021280/metformin-an-old-drug-for-the-treatment-of-diabetes-but-a-new-drug-for-the-protection-of-the-endothelium
#18
REVIEW
Mustafa Kinaan, Hong Ding, Chris R Triggle
The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or 'gold standard' drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial...
2015: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/25894929/disruption-of-basigin-decreases-lactic-acid-export-and-sensitizes-non-small-cell-lung-cancer-to-biguanides-independently-of-the-lkb1-status
#19
Sara Granja, Ibtissam Marchiq, Renaud Le Floch, Conceição Souto Moura, Fátima Baltazar, Jacques Pouysségur
Most cancers rely on aerobic glycolysis to generate energy and metabolic intermediates. To maintain a high glycolytic rate, cells must efficiently export lactic acid through the proton-coupled monocarboxylate transporters (MCT1/4). These transporters require a chaperone, CD147/BASIGIN (BSG) for trafficking to the plasma membrane and function.To validate the key role of these transporters in lung cancer, we first analysed the expression of MCT1/4 and BSG in 50 non-small lung cancer (NSCLC) cases. These proteins were specifically upregulated in tumour tissues...
March 30, 2015: Oncotarget
https://www.readbyqxmd.com/read/25867026/metformin-inhibits-growth-of-human-glioblastoma-cells-and-enhances-therapeutic-response
#20
Julie Sesen, Perrine Dahan, Sarah J Scotland, Estelle Saland, Van-Thi Dang, Anthony Lemarié, Betty M Tyler, Henry Brem, Christine Toulas, Elizabeth Cohen-Jonathan Moyal, Jean-Emmanuel Sarry, Nicolas Skuli
High-grade gliomas, glioblastomas (GB), are refractory to conventional treatment combining surgery, chemotherapy, mainly temozolomide, and radiotherapy. This highlights an urgent need to develop novel therapies and increase the efficacy of radio/chemotherapy for these very aggressive and malignant brain tumors. Recently, tumor metabolism became an interesting potential therapeutic target in various cancers. Accordingly, combining drugs targeting cell metabolism with appropriate chemotherapeutic agents or radiotherapy has become attractive...
2015: PloS One
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