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Metformin anti-cancer

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/29131265/metformin-reduces-satb2-mediated-osteosarcoma-stem-cell-like-phenotype-and-tumor-growth-via-inhibition-of-n-cadherin-nf-kb-signaling
#9
H Y Xu, W Fang, Z W Huang, J C Lu, Y Q Wang, Q L Tang, G H Song, Y Kang, X J Zhu, C Y Zou, H L Yang, J N Shen, J Wang
OBJECTIVE: To investigate the role of SATB2 in stem cell-like properties of osteosarcoma and identify new strategies to eliminate cancer stem cells of osteosarcoma. MATERIALS AND METHODS: Osteosarcoma cancer stem cells were derived by sarcosphere generation or chemo drug enrichment. SATB2 and pluripotency-associated gene expression in osteosarcoma CSCs were analyzed using qRT-PCR and Western blotting. The sphere formation assay, cell counting kit-8 assay and anti-chemotherapy proteins were used to measure the effects of altered SATB2, N-cadherin expression or metformin treatment in CSCs...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29093681/quantitative-and-systems-pharmacology-3-network-based-identification-of-new-targets-for-natural-products-enables-potential-uses-in-aging-associated-disorders
#10
Jiansong Fang, Li Gao, Huili Ma, Qihui Wu, Tian Wu, Jun Wu, Qi Wang, Feixiong Cheng
Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29073599/combination-of-solamargine-and-metformin-strengthens-igfbp1-gene-expression-through-inactivation-of-stat3-and-reciprocal-interaction-between-foxo3a-and-sp1
#11
Qing Tang, Fang Zheng, JingJing Wu, Qian Xiao, Liuning Li, Swei Sunny Hann
BACKGROUND/AIMS: Solamargine, one natural photochemical component from traditional plants, has been shown to have anti-cancers properties. We previously showed that solamargine inhibited the growth of non-small-cell lung cancer (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene and regulation of downstream signaling pathways. However, the detailed mechanism underlying this, especially in combination of metformin, a known AMPK activator, still remained to be determined...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29063073/the-association-between-metformin-use-and-colorectal-cancer-survival-among-patients-with-diabetes-mellitus-an-updated-meta-analysis
#12
Shan Tian, Hong-Bo Lei, Yu-Lan Liu, Yan Chen, Wei-Guo Dong
OBJECTIVE: Recent studies have reported conflicting results on the correlation between metformin use and outcomes in patients with colorectal cancer (CRC). A meta-analysis was performed to evaluate the efficacy of metformin therapy on the prognosis of CRC patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and the Web of Science for related articles up to August 2016. Two investigators independently identified and extracted information...
September 2017: Chronic Diseases and Translational Medicine
https://www.readbyqxmd.com/read/29059169/metformin-regulates-global-dna-methylation-via-mitochondrial-one-carbon-metabolism
#13
E Cuyàs, S Fernández-Arroyo, S Verdura, R Á-F García, J Stursa, L Werner, E Blanco-González, M Montes-Bayón, J Joven, B Viollet, J Neuzil, J A Menendez
The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/28979682/protopanaxadiol-and-metformin-synergistically-inhibit-estrogen-mediated-proliferation-and-anti-autophagy-effects-in-endometrial-cancer-cells
#14
Chun-Jie Gu, Jiao Cheng, Bing Zhang, Shao-Liang Yang, Feng Xie, Jian-Song Sun, Li-Qing Huang, Jin-Jin Yu, Ming-Qing Li
Metformin is commonly used for treating type II diabetes and has recently been reported to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. Ginsenosides are the main effective biological components of ginseng. It has been reported that ginsenoside-Rb2 inhibit the invasiveness of endometrial cancer cells (ECC). The aim of this study was to investigate whether protopanaxadiol (PPD, a metabolite of ginsenosides) and metformin could synergistically regulate the biological behavior of ECC and analyze its possible mechanism...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28977950/prognostic-significance-of-anti-diabetic-medications-in-pancreatic-cancer-a-meta-analysis
#15
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)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977926/redox-dependent-modulation-of-metformin-contributes-to-enhanced-sensitivity-of-esophageal-squamous-cell-carcinoma-to-cisplatin
#16
Pin Dong Li, Zhao Liu, Tian Tian Cheng, Wen Guang Luo, Jing Yao, Jing Chen, Zhen Wei Zou, Li Li Chen, Charlie Ma, Xiao Fang Dai
Glutathione is the major intracellular anti-oxidant against reactive oxygen species and serves as a detoxification essential. The anti-diabetic drug metformin has been showed to exert anti-tumor activity via modulation of redox homeostasis. In this study, we provided evidence that metformin inhibits proliferation and induces apoptosis of esophageal squamous cancer cells. Importantly, we found that metformin acts as pro-oxidant via depletion of intracellular glutathione. Co-treatment with metformin reversed the elevated intracellular glutathione induced by cisplatin and therefore enhanced the sensitivity to cisplatin in vitro and in vivo...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977822/blocking-epithelial-to-mesenchymal-transition-in-glioblastoma-with-a-sextet-of-repurposed-drugs-the-eis-regimen
#17
Richard E Kast, Nicolas Skuli, Georg Karpel-Massler, Guido Frosina, Timothy Ryken, Marc-Eric Halatsch
This paper outlines a treatment protocol to run alongside of standard current treatment of glioblastoma- resection, temozolomide and radiation. The epithelial to mesenchymal transition (EMT) inhibiting sextet, EIS Regimen, uses the ancillary attributes of six older medicines to impede EMT during glioblastoma. EMT is an actively motile, therapy-resisting, low proliferation, transient state that is an integral feature of cancers' lethality generally and of glioblastoma specifically. It is believed to be during the EMT state that glioblastoma's centrifugal migration occurs...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28964970/metformin-triggers-apoptosis-in-pel-cells-and-alters-bortezomib-induced-unfolded-protein-response-increasing-its-cytotoxicity-and-inhibiting-kshv-lytic-cycle-activation
#18
Marisa Granato, Maria Saveria Gilardini Montani, Maria Anele Romeo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Metformin, the most used drug for the treatment of diabetes type 2 patients, has been shown to have anti-cancer properties. In this study, we found that metformin induced apoptosis in Primary Effusion Lymphoma (PEL) cells, an aggressive B cell lymphoma associated with KSHV against which the conventional therapies usually fail. The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival...
December 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28962576/statistically-controlled-identification-of-differentially-expressed-genes-in-one-to-one-cell-line-comparisons-of-the-cmap-database-for-drug-repositioning
#19
Jun He, Haidan Yan, Hao Cai, Xiangyu Li, Qingzhou Guan, Weicheng Zheng, Rou Chen, Huaping Liu, Kai Song, Zheng Guo, Xianlong Wang
BACKGROUND: The Connectivity Map (CMAP) database, an important public data source for drug repositioning, archives gene expression profiles from cancer cell lines treated with and without bioactive small molecules. However, there are only one or two technical replicates for each cell line under one treatment condition. For such small-scale data, current fold-changes-based methods lack statistical control in identifying differentially expressed genes (DEGs) in treated cells. Especially, one-to-one comparison may result in too many drug-irrelevant DEGs due to random experimental factors...
September 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28947975/phenformin-inhibits-growth-and-epithelial-mesenchymal-transition-of-erbb2-overexpressing-breast-cancer-cells-through-targeting-the-igf1r-pathway
#20
Zhiying Guo, Ming Zhao, Erin W Howard, Qingxia Zhao, Amanda B Parris, Zhikun Ma, Xiaohe Yang
Reports suggest that metformin, a popular anti-diabetes drug, prevents breast cancer through various systemic effects, including insulin-like growth factor receptor (IGFR) regulation. Although the anti-cancer properties of metformin have been well-studied, reports on a more bioavailable/potent biguanide, phenformin, remain sparse. Phenformin exerts similar functional activity to metformin and has been reported to impede mammary carcinogenesis in rats. Since the effects of phenformin on specific breast cancer subtypes have not been fully explored, we used ErbB2-overexpressing breast cancer cell and animal models to test the anti-cancer potential of phenformin...
September 1, 2017: Oncotarget
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