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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28979682/protopanaxadiol-and-metformin-synergistically-inhibit-estrogen-mediated-proliferation-and-anti-autophagy-effects-in-endometrial-cancer-cells
#1
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
#2
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
#3
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
#4
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
#5
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...
September 28, 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
#6
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
#7
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
https://www.readbyqxmd.com/read/28936567/metformin-as-a-repurposed-therapy-in-advanced-non-small-cell-lung-cancer-nsclc-results-of-a-phase-ii-trial
#8
Anish B Parikh, Peter Kozuch, Nicholas Rohs, Daniel J Becker, Benjamin P Levy
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity...
September 22, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28933290/nutraceuticals-and-repurposed-drugs-of-phytochemical-origin-in-prevention-and-interception-of-chronic-degenerative-disease-and-cancer
#9
Adriana Albini, Barbara Bassani, Denisa Baci, Katiuscia Dallaglio, Matteo Gallazzi, Paola Corradino, Antonino Bruno, Douglas M Noonan
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28926637/selective-cytotoxicity-of-the-anti-diabetic-drug-metformin-in-glucose-deprived-chicken-dt40-cells
#10
Kei Kadoda, Takahito Moriwaki, Masataka Tsuda, Hiroyuki Sasanuma, Masamichi Ishiai, Minoru Takata, Hiroshi Ide, Shin-Ichiro Masunaga, Shunichi Takeda, Keizo Tano
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity...
2017: PloS One
https://www.readbyqxmd.com/read/28915708/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
#11
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900501/metformin-sensitizes-leukemia-cells-to-vincristine-via-activation-of-amp-activated-protein-kinase
#12
Yong Yi, Linfeng Gao, Min Wu, Juan Ao, Chunyan Zhang, Xiaodong Wang, Min Lin, Johann Bergholz, Yujun Zhang, Zhi-Xiong Jim Xiao
Vincristine is extensively used chemotherapeutic medicine to treat leukemia. However, it remains a critical clinical problem with regard to its toxicity and drug-resistance. AMP-activated protein kinase (AMPK) is an energy sensor that is pivotal in maintaining cell metabolic homeostasis. It is reported that AMPK is involved in vincristine-induced apoptosis. However, whether AMPK is involved in chemotherapy-resistance is largely unclear. It is well-documented that metformin, a widely used medicine to treat type II diabetes, possesses anti-cancer activities, yet whether metformin affects leukemia cell viability via vincristine is unknown...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900491/the-clinical-effect-of-metformin-on-the-survival-of-lung-cancer-patients-with-diabetes-a-comprehensive-systematic-review-and-meta-analysis-of-retrospective-studies
#13
Xun Cao, Zhe-Sheng Wen, Xu-Dong Wang, Yong Li, Kui-Yuan Liu, Xin Wang
Preclinical investigations have revealed an anti-cancer effect of metformin. Several studies of metformin treatment have demonstrated the improved clinical outcomes of lung cancer patients with diabetes; however, the results have been inconsistent among studies. Our systematic review and meta-analysis aimed to summarize the up-to-date effects of metformin on diabetic lung cancer patients. A systematic search was performed for studies published. Then, these studies were evaluated for inclusion, and relevant data was extracted...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28881582/metformin-requires-4e-bps-to-induce-apoptosis-and-repress-translation-of-mcl-1-in-hepatocellular-carcinoma-cells
#14
Mamatha Bhat, Akiko Yanagiya, Tyson Graber, Nataliya Razumilava, Steve Bronk, Domenick Zammit, Yunhao Zhao, Chadi Zakaria, Peter Metrakos, Michael Pollak, Nahum Sonenberg, Gregory Gores, Maritza Jaramillo, Masahiro Morita, Tommy Alain
Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC). Metformin has also been shown to induce apoptosis in this cancer. Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs). Further, we ask whether changes in 4E-BPs activity during metformin treatment negatively regulate translation of the anti-apoptotic myeloid cell leukemia 1 (Mcl-1) mRNA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28875433/crucial-micrornas-and-genes-in-metformin-s-anti-pancreatic-cancer-effect-explored-by-microrna-mrna-integrated-analysis
#15
Yilong Li, Le Li, Guangquan Zhang, Yongwei Wang, Hua Chen, Rui Kong, Shangha Pan, Bei Sun
Despite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their target mRNAs...
September 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28842630/results-from-11-c-metformin-pet-scans-tissue-analysis-and-cellular-drug-sensitivity-assays-questions-the-view-that-biguanides-affects-tumor-respiration-directly
#16
Ane B Iversen, Michael R Horsman, Steen Jakobsen, Jonas B Jensen, Christian Garm, Niels Jessen, Peter Breining, Jørgen Frøkiær, Morten Busk
The anti-diabetic biguanide drugs metformin (METF) and phenformin (PHEN) may have anti-cancer effects. Biguanides suppress plasma growth factors, but nonetheless, the view that these mitochondrial inhibitors accumulate in tumor tissue to an extent that leads to severe energetic stress or alleviation of hypoxia-induced radioresistance is gaining ground. Our cell studies confirm that biguanides inhibits cell proliferation by targeting respiration, but only at highly suprapharmacological concentrations due to low drug retention...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840963/the-enhancement-of-combination-of-berberine-and-metformin-in-inhibition-of-dnmt1-gene-expression-through-interplay-of-sp1-and-pdpk1
#17
Fang Zheng, JingJing Wu, Qing Tang, Qian Xiao, WanYin Wu, Swei Sunny Hann
Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti-cancer properties. We have showed that BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a). However, the in-depth mechanism underlying the anti-tumor effects still remained to be elucidated. Herein, we further confirmed that BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells. Mechanistically, we observed that BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28837141/metformin-reverses-prostate-cancer-resistance-to-enzalutamide-by-targeting-tgf-%C3%AE-1-stat3-axis-regulated-emt
#18
Qiuli Liu, Dali Tong, Gaolei Liu, Jing Xu, Khang Do, Kyla Geary, Dianzheng Zhang, Jun Zhang, Yao Zhang, Yaoming Li, Gang Bi, Weihua Lan, Jun Jiang
Although the newly developed second-generation anti-androgen drug enzalutamide can repress prostate cancer progression significantly, it only extends the survival of prostate cancer patients by 4-6 months mainly due to the occurrence of enzalutamide resistance. Most of the previous studies on AR antagonist resistance have been focused on AR signaling. Therefore, the non-AR pathways on enzalutamide resistance remain largely unknown. By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28827783/ccdc3-a-new-p63-target-involved-in-regulation-of-liver-lipid-metabolism
#19
Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X Zeng, Hua Lu
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822889/metformin-targets-gastric-cancer-stem-cells
#20
Sarah Courtois, Raúl V Durán, Julie Giraud, Elodie Sifré, Julien Izotte, Francis Mégraud, Philippe Lehours, Christine Varon, Emilie Bessède
Gastric cancer is the third leading cause of cancer-related deaths worldwide and has still a poor prognosis. Therefore, new therapeutic strategies are needed: among them, targeting cancer stem cells (CSCs) could offer new opportunities. The aim of our study was to evaluate the anti-tumoural effect of metformin on gastric cancer in vitro and in vivo and especially, to determine whether this molecule could target the gastric CSCs. Metformin effects were evaluated on the proliferation and tumourigenic properties of the gastric CSCs from patient-derived primary tumour xenografts (PDXs) and cancer cell lines (MKN45, AGS and MKN74) in vitro in conventional 2 dimensional (2D) and in 3 dimensional (3D) culture systems, in which only CSCs are able to form tumourspheres and in mouse xenograft models in vivo...
October 2017: European Journal of Cancer
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