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Metformin anti-cancer

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https://www.readbyqxmd.com/read/29423103/metformin-induces-distinct-bioenergetic-and-metabolic-profiles-in-sensitive-versus-resistant-high-grade-serous-ovarian-cancer-and-normal-fallopian-tube-secretory-epithelial-cells
#1
Melissa Hodeib, Martin P Ogrodzinski, Laurent Vergnes, Karen Reue, Beth Y Karlan, Sophia Y Lunt, Paul-Joseph P Aspuria
Metformin is a widely used agent for the treatment of diabetes and infertility, however, it has been found to have anti-cancer effects in a variety of malignancies including high grade serous ovarian cancer (HGSC). Studies describing the mechanisms by which metformin affects HGSC are ongoing, but detailed analysis of its effect on the cellular metabolism of both HGSC cells and their precursor, normal fallopian tube secretory epithelial cells (FTSECs), is lacking. We addressed the effects of metformin and the more potent biguanide, phenformin, on HGSC cell lines and normal immortalized FTSECs...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416677/identification-of-human-age-associated-gene-co-expressions-in-functional-modules-using-liquid-association
#2
Jialiang Yang, Yufang Qin, Tiantian Zhang, Fayou Wang, Lihong Peng, Lijuan Zhu, Dawei Yuan, Pan Gao, Jujuan Zhuang, Zhongyang Zhang, Jun Wang, Yun Fang
Aging is a major risk factor for age-related diseases such as certain cancers. In this study, we developed Age Associated Gene Co-expression Identifier (AAGCI), a liquid association based method to infer age-associated gene co-expressions at thousands of biological processes and pathways across 9 human tissues. Several hundred to thousands of gene pairs were inferred to be age co-expressed across different tissues, the genes involved in which are significantly enriched in functions like immunity, ATP binding, DNA damage, and many cancer pathways...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397734/unique-features-of-metformin-a-combined-experimental-theoretical-and-simulation-study-of-its-structure-dynamics-and-interaction-energetics-with-dna-grooves
#3
Sayantan Mondal, Rudra Narayan Samajdar, Saumyak Mukherjee, Aninda Jiban Bhattacharyya, Biman Bagchi
There are certain small molecules that exhibit extraordinarily diverse biological activities. Metformin is one of them. It is widely used as anti-diabetic drug for type-two diabetes. Recent evidences of its role in anti-tumour activities and increasing the survival rates of cancer patients (namely colorectal, breast, pancreas and prostate cancer) are emerging. However, theoretical studies of structure and dynamics of metformin have not yet been fully explored. In this work, we investigate the characteristic structural and dynamical features of three mono-protonated forms of metformin hydrochloride with the help of experiments, quantum chemical calculations and atomistic molecular dynamics simulations...
February 3, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29396886/the-anti-tumor-effects-of-metformin-are-due-to-inhibiting-nf-%C3%AE%C2%BAb-nuclear-translocation-in-esophageal-squamous-cell-carcinoma
#4
Nobufumi Sekino, Masayuki Kano, Yasunori Matsumoto, Haruhito Sakata, Yasunori Akutsu, Naoyuki Hanari, Kentaro Murakami, Takeshi Toyozumi, Masahiko Takahashi, Ryota Otsuka, Masaya Yokoyama, Tadashi Shiraishi, Koichiro Okada, Isamu Hoshino, Keiko Iida, Aki Komatsu Akimoto, Hisahiro Matsubara
Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and the new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial...
February 3, 2018: Cancer Science
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#5
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#6
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29329345/survival-benefit-associated-with-metformin-use-in-inoperable-non-small-cell-lung-cancer-patients-with-diabetes-a-population-based-retrospective-cohort-study
#7
Min-Chun Chuang, Yao-Hsu Yang, Ying-Huang Tsai, Meng-Jer Hsieh, Yu-Ching Lin, Chin-Kuo Lin, Pau-Chung Chen, Tsung-Ming Yang
OBJECTIVE: To evaluate the effects of metformin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients with diabetes using the Taiwanese National Health Insurance Research Database. RESEARCH DESIGN AND METHODS: In total, 7,620 patients were eligible in this study, among them, 3,578 patients were metformin users and 4,042 were non-users. Propensity score matching was used to reduce possible confounding factors. In total, 4,182 patients (2,091 matched pairs) were included in the matched cohort...
2018: PloS One
https://www.readbyqxmd.com/read/29284782/cytotoxic-activity-of-metformin-in-vitro-does-not-correlate-with-its-antitumor-action-in-vivo
#8
O N Pyaskovskaya, D L Kolesnik, A G Fedorchuk, G V Gorbik, G I Solyanik
It is known that metformin is a hypoglycemic drug used to treat type II diabetes mellitus. Recently active studies of its antitumor activity in relation to different types of malignant cells are conducted. AIM: To determine the relationship between cytotoxic activity of metformin in vitro and its antitumor activity in vivo. MATERIALS AND METHODS: The rat C6 glioma cell line and mouse Lewis lung carcinoma cells (LLC) were used in this work. The number of living cells in the cytotoxic test was evaluated using sulforhodamine B...
December 2017: Experimental Oncology
https://www.readbyqxmd.com/read/29274360/disulfiram-with-or-without-metformin-inhibits-oesophageal-squamous-cell-carcinoma-in%C3%A2-vivo
#9
Rupal Jivan, Jade Peres, Leonard Howard Damelin, Reubina Wadee, Robin Bruce Veale, Sharon Prince, Demetra Mavri-Damelin
Oesophageal squamous cell carcinoma (OSCC) is highly prevalent in developing countries but there has been little recent progress into efficacious yet affordable treatment strategies. Drug repurposing is one attractive approach for cancer therapy. Disulfiram (DSF), used to treat alcoholism, inhibits cancer growth and we previously found that DSF perturbs protein degradation/turnover pathways in vitro. This was enhanced by combining DSF with the anti-diabetic drug metformin (Met). Here, we investigated DSF with/without Met, against OSCC in vivo...
March 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29274299/anti-proliferative-effect-of-rosiglitazone-in-the-human-t-lymphocyte-leukaemia-cell-line-jurkat-cells
#10
Rui Wei, Fei Yu, Jin Yang, Hongwei Gao, Haining Wang, Tianpei Hong
Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in various types of human cancer cells including leukaemia cells, and activation of PPARγ can inhibit cancer cell growth. However, whether PPARγ is expressed in Jurkat cells, a human T-lymphocyte leukaemia cell line, and whether activation of PPARγ affects cell biological behaviours remains to be clarified. In this study, we investigated the effect of a PPARγ activator rosiglitazone, under clinically relevant pharmacological concentrations, on the growth and apoptosis of Jurkat cells in vitro and explored the possible mechanism...
December 23, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29248761/low-dose-metformin-exposure-causes-changes-in-expression-of-endocrine-disruption-associated-genes
#11
Nicholas J Niemuth, Rebecca D Klaper
The presence of intersex fish in watersheds around the world is a warning of the presence of anthropogenic endocrine-disrupting compounds (EDCs) being deposited into the aquatic environment. The anti-diabetic drug metformin is among the most prevalent and ubiquitous of the myriad pharmaceuticals found in wastewater effluent and watersheds worldwide. In addition to its prescription for type-2 diabetes, metformin is indicated as a treatment in cancers and the endocrine disorder polycystic ovarian syndrome (PCOS)...
December 8, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29245964/phenformin-has-anti-tumorigenic-effects-in-human-ovarian-cancer-cells-and-in-an-orthotopic-mouse-model-of-serous-ovarian-cancer
#12
Amanda L Jackson, Wenchuan Sun, Joshua Kilgore, Hui Guo, Ziwei Fang, Yajie Yin, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29230104/metformin-sensitizes-non-small-cell-lung-cancer-cells-to-an-epigallocatechin-3-gallate-egcg-treatment-by-suppressing-the-nrf2-ho-1-signaling-pathway
#13
Chenxiao Yu, Yang Jiao, Jiao Xue, Qi Zhang, Hongying Yang, Ligang Xing, Guangxia Chen, Jinchang Wu, Shuyu Zhang, Wei Zhu, Jianping Cao
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29226720/memantine-induces-apoptosis-and-inhibits-cell-cycle-progression-in-lncap-prostate-cancer-cells
#14
G Albayrak, E Konac, A U Dikmen, C Y Bilen
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29212192/vorinostat-and-metformin-sensitize-egfr-tki-resistant-nsclc-cells-via-bim-dependent-apoptosis-induction
#15
Hengyi Chen, Yubo Wang, Caiyu Lin, Conghua Lu, Rui Han, Lin Jiao, Li Li, Yong He
There is a close relationship between low expression of BIM and resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Vorinostat is a pan-histone deacetylase inhibitor (HDACi) that augments BIM expression in various types of tumor cells, however, this effect is attenuated by the high expression of anti-apoptotic proteins in EGFR-TKI resistant non-small cell lung cancer (NSCLC) cells. Vorinostat in combination with metformin - a compound that can inhibit anti-apoptotic proteins expression, might cooperate to activate apoptotic signaling and overcome EGFR-TKI resistance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#16
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29189123/anti-aging-drugs-prospect-of-longer-life
#17
Blanka Klimova, Michal Novotny, Kamil Kuca
BACKGROUND: Aging is a natural part of human life. However, recent discoveries indicate that pharmacological approaches used for the improvement and possibly, for the delay of the aging process, might shed a new light on this topic. This might obviously contribute to the extension of the active life of older people and maintenance of their quality of life, which could consequently reduce both social and economic burden of each country, especially the developed ones. OBJECTIVE: The purpose of this study is to explore pharmacological discoveries which may help to the delay or improvement of the aging process...
November 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29182407/metformin-is-associated-with-reduced-cell-proliferation-in-human-endometrial-cancer-by-inbibiting-pi3k-akt-mtor-signaling
#18
Yan Zhao, Hongli Sun, Minjuan Feng, Jinyan Zhao, Xiaogui Zhao, Qiuyuan Wan, Dongge Cai
Metformin recently gained traction as potential anti-endometrial cancer agent for its new applications. However, the underlying mechanisms of the anti-cancer effect of metformin in the endometrial cancer have not yet been fully elucidated. Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33) and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were recruited as controls. We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining...
November 28, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#19
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29165314/towards-natural-mimetics-of-metformin-and-rapamycin
#20
Alexander Aliper, Leslie Jellen, Franco Cortese, Artem Artemov, Darla Karpinsky-Semper, Alexey Moskalev, Andrew G Swick, Alex Zhavoronkov
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects...
November 15, 2017: Aging
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