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Cancer AND Metformin AND Mitochondria

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https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#1
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael B Dwinell
Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells...
April 21, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#2
REVIEW
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael Dwinell
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential...
April 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#3
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28114961/mif-cd74-axis-is-a-target-for-novel-therapies-in-colon-carcinomatosis
#4
Fabio Bozzi, Angela Mogavero, Luca Varinelli, Antonino Belfiore, Giacomo Manenti, Claudio Caccia, Chiara C Volpi, Galina V Beznoussenko, Massimo Milione, Valerio Leoni, Annunziata Gloghini, Alexandre A Mironov, Ermanno Leo, Silvana Pilotti, Marco A Pierotti, Italia Bongarzone, Manuela Gariboldi
BACKGROUND: Strategies aimed at obtaining a complete cytoreduction are needed to improve long-term survival for patients with colorectal cancer peritoneal carcinomatosis (CRC-pc). METHODS: We established organoid models from peritoneal metastases of two naïve CRC patients. A standard paraffin inclusion was conducted to compare their 3D structure and immunohistochemical profile with that of the corresponding surgical samples. RNA expression levels of the CRC stem cell marker LGR5 was measured by in situ hybridization...
January 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27746051/metformin-targets-central-carbon-metabolism-and-reveals-mitochondrial-requirements-in-human-cancers
#5
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...
November 8, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27216187/mitochondria-targeted-analogues-of-metformin-exhibit-enhanced-antiproliferative-and-radiosensitizing-effects-in-pancreatic-cancer-cells
#6
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
#7
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
#8
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
#9
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
#10
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...
April 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26625127/metformin-antagonizes-cancer-cell-proliferation-by-suppressing-mitochondrial-dependent-biosynthesis
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
May 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/26215782/metformin-and-prostate-cancer-stem-cells-a-novel-therapeutic-target
#18
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
#19
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
#20
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
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