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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28533491/prognostic-significance-of-anti-diabetic-medications-in-pancreatic-cancer-a-meta-analysis
#1
Dong-Chu Zhou, Hui Gong, Chong-Qing Tan, Jian-Quan Luo
The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#2
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#3
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#4
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/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#5
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
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
#6
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/28481268/metformin-in-lung-cancer-review-of-in-vitro-and-in-vivo-animal-studies
#7
REVIEW
Michael Yousef, Evangelia Tsiani
Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival and these mutations allow them to develop resistance to many chemotherapeutic agents, highlighting the need for development of new potent anti-cancer agents. Metformin has long been used as a treatment for type 2 diabetes and has recently attracted attention as a potential agent to be used in the treatment of cancer...
May 6, 2017: Cancers
https://www.readbyqxmd.com/read/28459432/metformin-inhibits-suv39h1-mediated-migration-of-prostate-cancer-cells
#8
T Yu, C Wang, J Yang, Y Guo, Y Wu, X Li
Prostate cancer (PCa) is a leading cause of cancer-related death among men, largely due to incurable distant metastases. Metformin, the most common used anti-type-2 diabetes medicine, has been linked to reduced cancer risk and better diagnosis. We found that metformin was able to inhibit PCa cell migration, which correlates with tumor metastatic capability. The pathogenesis and progression of tumors are closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications...
May 1, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28459206/metformin-augments-doxorubicin-cytotoxicity-in-mammary-carcinoma-through-activation-of-adenosine-monophosphate-protein-kinase-pathway
#9
Nahla E El-Ashmawy, Naglaa F Khedr, Hoda A El-Bahrawy, Hend E Abo Mansour
Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28445955/metformin-is-associated-with-survival-benefit-in-pancreatic-cancer-patients-with-diabetes-a-systematic-review-and-meta-analysis
#10
Ping-Ting Zhou, Bo Li, Fu-Rao Liu, Mei-Chao Zhang, Qian Wang, Yan-Yan Li, Ci Xu, Yuan-Hua Liu, Yuan Yao, Dong Li
BACKGROUND: Pancreatic cancer is a highly lethal disease with a poor prognosis while metformin has been associated with a decreased risk of pancreatic cancer. Although the benefit of metformin was observed for pancreatic cancer prevention, it is not clear whether it can also affect the survival of pancreatic cancer patients with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted to assess the effect of metformin on the survival of pancreatic cancer patients with type 2 diabetes mellitus...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444639/metformin-and-prostate-cancer-a-new-role-for-an-old-drug
#11
REVIEW
Jessica Whitburn, Claire M Edwards, Prasanna Sooriakumaran
PURPOSE OF REVIEW: Since epidemiological studies first demonstrated a potential positive effect of metformin in reducing cancer incidence and mortality, there has been an increased interest in not only better understanding metformin's mechanisms of action but also in exploring its potential anti-cancer effects. In this review, we aim to summarise the current evidence exploring a role for metformin in prostate cancer therapy. RECENT FINDINGS: Preclinical studies have demonstrated a number of antineoplastic biological effects via a range of molecular mechanisms...
June 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28443209/metformin-prevents-hormonal-and-metabolic-disturbances-and-1-2-dimethylhydrazine-induced-colon-carcinogenesis-in-non-diabetic-rats
#12
Viktoria V Bekusova, Vasily M Patsanovskii, Alexander D Nozdrachev, Alexandr P Trashkov, Margarita R Artemenko, Vladimir N Anisimov
Effects of two doses of the anti-diabetic drug, metformin (MF), on hormonal and metabolic levels of serum of non-diabetic male Wistar rats with 1,2-dimethylhydrazine (DMH)-induced colon tumor adenocarcinomas were studied. Carcinogenesis in the animals was also observed. Rats with DMH-induced colon adenocarcinomas had elevated levels of serum glucose, insulin, insulin-like growth factor-1, total cholesterol, triglycerides, catalase, malonic dialdehyde, glycated hemoglobin, aspartate aminotransferase, and alanine aminotransferase and decreased hemoglobin...
February 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28407669/metformin-inhibits-n-methyl-n-nitrosourea-induced-gastric-tumorigenesis-in-db-db-mice
#13
Shan Zhuang, Yongmei Jian, Yongning Sun
Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group)...
April 13, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28406985/metformin-inhibited-esophageal-squamous-cell-carcinoma-proliferation-in-vitro-and-in-vivo-and-enhanced-the-anti-cancer-effect-of-cisplatin
#14
Feng Wang, Xianfei Ding, Tao Wang, Zhengzheng Shan, Jun Wang, Shaoxuan Wu, Yanyan Chi, Yana Zhang, Zhuan Lv, Liuxing Wang, Qingxia Fan
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis in China. Chemotherapy now is one of the most frequently used treatments for patients with ESCC in middle or late stage, however the effects were often limited by increased chemoresistance or treatment toxicity. So it is urgent to find new drugs to treat ESCC patients. Metformin with low cost and toxicity has proved to have anti-cancer effects in a numerous cancers, while its role and mechanism in ESCC has seldom been studied...
2017: PloS One
https://www.readbyqxmd.com/read/28392858/effect-of-metformin-on-different-non-diabetes-related-conditions-a-special-focus-on-malignant-conditions-review-of-literature
#15
REVIEW
Elamin Abdelgadir, Razan Ali, Fauzia Rashid, Alaaeldin Bashier
Metformin has been proven to be one of the most safe and effective antihyperglycemic agents. Through more than six decades of metformin use, it became the most studied hypoglycemic agent; through these studies, it showed a marvelous non-glycemic related effect. These effects include modulation of different points of cancer timeline, weight reduction, cardiovascular health, thyroid diseases, polycystic ovaries disease and many other medical conditions. The aim of this review was to assess the effect of metformin on non-diabetes related medical diseases...
May 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28391030/metformin-triggers-autophagy-to-attenuate-drug-induced-apoptosis-in-nsclc-cells-with-minor-effects-on-tumors-of-diabetic-patients
#16
Zhiguang Xiao, Silvia Gaertner, Alicia Morresi-Hauf, Rebecca Genzel, Thomas Duell, Axel Ullrich, Pjotr G Knyazev
The biologic plausibility of an association between type 2 diabetes mellitus (T2D) and lung cancer has received increasing attention, but the results of investigations remain largely inconclusive. In the present study we investigated the influence of the anti-diabetic drug metformin on the cytotoxic effects of EGFR targeted therapy and chemotherapy in 7 non-small cell lung cancer (NSCLC) cell lines and a cohort of lung cancer patients with/without T2D. In vitro cell viability assays indicated that metformin didn't potentiate the growth inhibitory effects of erlotinib at different doses in cell lines that are of distinct genetic background...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28387573/metformin-inhibits-rankl-and-sensitizes-cancer-stem-cells-to-denosumab
#17
Elisabet Cuyàs, Begoña Martin-Castillo, Joaquim Bosch-Barrera, Javier A Menendez
The increased propensity of BRCA1 mutation carriers to develop aggressive breast tumors with stem-like properties begins to be understood in terms of osteoprotegerin (OPG)-unrestricted cross-talk between RANKL-overproducing progesterone-sensor cells and cancer-initiating RANK(+) responder cells that reside within pre-malignant BRCA1(mut/+) breast epithelial tissue. We recently proposed that, in the absence of hormone influence, cancer-initiating cells might remain responsive to RANKL stimulation, and hence to the therapeutic effects of the anti-RANKL antibody denosumab because genomic instability induced by BRCA1 haploinsufficiency might suffice to cell-autonomously hyperactivate RANKL gene expression...
April 7, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28385910/metformin-reduces-prostate-tumor-growth-in-a-diet-dependent-manner-by-modulating-multiple-signaling-pathways
#18
Andre Sarmento-Cabral, Fernando L-Lopez, Manuel D Gahete, Justo P Castano, Raul M Luque
Prostate-cancer is strongly influenced by obesity, wherein metformin could represent a promising treatment; however, the endocrine-metabolic/cellular/molecular-mechanisms underlying these associations and effects are still unclear. To determine the beneficial anti-tumoral effects of metformin on prostate-cancer progression/aggressiveness and the relative contribution of high-fat diet (HFD; independently of obesity), we used HFD-fed immuno-suppressed mice inoculated with PC3 cells (which exhibited partial resistance to diet-induced obesity) compared with low-fat diet (LFD)-fed control-mice...
April 6, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#19
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/28373897/new-insight-for-metformin-against-bladder-cancer
#20
REVIEW
Amr Ahmed El-Arabey
International Agency for Research on Cancer (IARC) estimated that bladder cancer is the ninth most common cancer in the world, with 430,000 new cases and 165,000 deaths in 2012. Bladder cancer represents the fourth most common cancer in men and ninth most common cancer in women. It is the second most prevalent cancer in men 60 years of age or older in United States. Looking further down, continuing advancements in cancer research could potentially offer more choices for clinician and patient with longer survival and better quality of life...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
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