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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28052934/fixed-dose-combinations-of-pioglitazone-and-metformin-for-lung-cancer-prevention
#1
Donna E Seabloom, Arthur R Galbraith, Anna M Haynes, Jennifer D Antonides, Beverly R Wuertz, Wendy A Miller, Kimberly A Miller, Vernon E Steele, Mark Steven Miller, Margie L Clapper, M Gerard O'Sullivan, Frank G Ondrey
Combination treatment with pioglitazone and metformin are utilized clinically in the treatment of type II diabetes. Treatment with this drug combination reduced the development of aerodigestive cancers in this patient population. Our goal is to expand this treatment into clinical lung cancer chemoprevention. We hypothesized that dietary delivery of metformin/pioglitazone would prevent lung adenoma formation in A/J mice in a B[a]P-induced carcinogenesis model while modulating chemoprevention and anti-inflammatory biomarkers in residual adenomas...
January 4, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28045889/metformin-induces-growth-inhibition-and-cell-cycle-arrest-by-upregulating-microrna34a-in-renal-cancer-cells
#2
Wei Xie, Lei Wang, Halei Sheng, Jing Qiu, Di Zhang, Le Zhang, Fan Yang, Dahai Tang, Kebin Zhang
BACKGROUND Metformin is a widely used biguanide drug for the treatment of type 2 diabetes. It has been revaluated as a potential anti-cancer drug with promising activity in various tumors. However, the precise mechanisms underlying the suppression of cancer cells by metformin remain not well understood. MATERIAL AND METHODS In this study, human renal cell carcinoma cell line ACHN was used to investigate the anti-proliferation effect of metformin. A cell counting kit-8 assay was used to detect the cell viability...
January 3, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28043910/metformin-inhibits-castration-induced-emt-in-prostate-cancer-by-repressing-cox2-pge2-stat3-axis
#3
Dali Tong, Qiuli Liu, Gaolei Liu, Jing Xu, Weihua Lan, Yao Jiang, Hualiang Xiao, Dianzheng Zhang, Jun Jiang
Castration is the standard therapeutic treatment for advanced prostate cancer but with limited benefit due to the profound relapse and metastasis. Activation of inflammatory signaling pathway and initiation of epithelial-mesenchymal transition (EMT) are closely related to drug resistance, tumor relapseas well as metastasis. In this study, we demonstrated that metformin is capable of inhibiting prostate cancer cell migration and invasion by repressing EMT evidenced by downregulating the mesenchymal markers N-cadherin, Vimentin, and Twist and upregulating the epithelium E-cadherin...
December 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28036292/therapeutic-potential-of-the-metabolic-modulator-phenformin-in-targeting-the-stem-cell-compartment-in-melanoma
#4
Tiziana Petrachi, Alessandra Romagnani, Adriana Albini, Caterina Longo, Giuseppe Argenziano, Giulia Grisendi, Massimo Dominici, Alessia Ciarrocchi, Katiuscia Dallaglio
Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#5
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28011481/metformin-exerts-antiproliferative-and-anti-metastatic-effects-against-cholangiocarcinoma-cells-by-targeting-stat3-and-nf-%C3%A4-b
#6
Charupong Saengboonmee, Wunchana Seubwai, Ubon Cha'on, Kanlayanee Sawanyawisuth, Sopit Wongkham, Chaisiri Wongkham
BACKGROUND/AIM: Cholangiocarcinoma (CCA) is an aggressive cancer for which standard treatments are still ineffective. This study demonstrated the antiproliferative and anti-metastatic activity of metformin, an anti-diabetic drug, in CCA cells. MATERIALS AND METHODS: Cell proliferation, migration/invasion and anoikis resistance were determined. The underlying mechanisms were identified using western blotting and immunocytofluorescence. RESULTS: Metformin significantly suppressed proliferation of CCA cells in a dose- and time-dependent manner, regardless of glucose present in the medium...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/27990091/novel-applications-of-cox-2-inhibitors-metformin-and-statins-for-the-primary-chemoprevention-of-breast-cancer
#7
REVIEW
Darren Micallef, Sarah Micallef, Pierre Schembri-Wismayer, Jean Calleja-Agius
Recent evidence shows that commonly prescribed drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), metformin, and statins, may have beneficial roles in the primary chemoprevention of breast cancer. Therefore, these drugs could potentially be used in addition to the hormonal drugs currently used for this purpose (namely, selective estrogen receptor modulators and aromatase inhibitors) due to their alternative mechanisms of action.
2016: Journal of the Turkish German Gynecological Association
https://www.readbyqxmd.com/read/27959931/mate2-expression-is-associated-with-cancer-cell-response-to-metformin
#8
Sanjana Chowdhury, Eric Yung, Melania Pintilie, Hala Muaddi, Selim Chaib, ManTek Yeung, Manlio Fusciello, Jenna Sykes, Bethany Pitcher, Anna Hagenkort, Trevor McKee, Ravi Vellanki, Eric Chen, Robert G Bristow, Bradly G Wouters, Marianne Koritzinsky
BACKGROUND: There is great interest in repurposing the commonly prescribed anti-diabetic drug metformin for cancer therapy. Intracellular uptake and retention of metformin is affected by the expression of organic cation transporters (OCT) 1-3 and by multidrug and toxic compound extrusion (MATE) 1-2. Inside cells, metformin inhibits mitochondrial function, which leads to reduced oxygen consumption and inhibition of proliferation. Reduced oxygen consumption can lead to improved tumor oxygenation and radiation response...
2016: PloS One
https://www.readbyqxmd.com/read/27939359/a-story-of-metformin-butyrate-synergism-to-control-various-pathological-conditions-as-a-consequence-of-gut-microbiome-modification-genesis-of-a-wonder-drug
#9
REVIEW
Kunal Maniar, Amal Moideen, Ankur Mittal, Amol Patil, Amitava Chakrabarti, Dibyajyoti Banerjee
The most widely prescribed oral anti-diabetic agent today in the world today is a member of the biguanide class of drugs called metformin. Apart from its use in diabetes, it is currently being investigated for its potential use in many diseases such as cancer, cardiovascular diseases, Alzheimer's disease, obesity, comorbidities of diabetes such as retinopathy, nephropathy to name a few. Numerous in-vitro and in-vivo studies as well as clinical trials have been and are being conducted with a vast amount of literature being published every day...
December 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27919710/the-transcription-factor-carbohydrate-response-element-binding-protein-chrebp-a-possible-link-between-metabolic-disease-and-cancer
#10
REVIEW
Katsumi Iizuka
Carbohydrate-response element-binding protein (ChREBP) has been identified as a transcription factor that binds to carbohydrate response element in the promoter of pyruvate kinase, liver and red blood cells. ChREBP is activated by metabolites derived from glucose and suppressed by adenosine monophosphate (AMP), ketone bodies and cyclic cAMP. ChREBP regulates gene transcription related to glucose and lipid metabolism. Findings from knockout mice and human subjects suggest that ChREBP helps to induce hepatic steatosis, dyslipidemia, and glucose intolerance...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27919208/is-metformin-a-therapeutic-paradigm-for-colorectal-cancer-insight-into-the-molecular-pathway
#11
Zar Chii Thent, Nurul Hannim Zaidun, Fairuz Azmi, Mu Izuddin Senin, Haszianaliza Haslan, Ahmad Ruzain Salehuddin
Colorectal cancer (CRC) remains one of the major leading causes of cancer related morbidity and mortality. Apart from the conventional anti-neoplastic agents, metformin, a biguanide anti-diabetic agent, has recently found to have anti-cancer property. Several studies observed the effect of metformin towards its anti-cancer effect on colon or colorectal cancer in diabetic patients. However, only a few studies showed its effect on colorectal cancer in relation to the non-diabetic status. The present review aimed to highlight the insight into the molecular pathway of metformin towards colorectal cancer in the absence of diabetes mellitus...
December 5, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27916907/metformin-inhibits-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-via-pkm2-relative-mtor-p70s6k-signaling-pathway-in-cervical-carcinoma-cells
#12
Keyan Cheng, Min Hao
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. METHODS: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27904682/targeting-cancer-cell-metabolism-the-combination-of-metformin-and-2-deoxyglucose-regulates-apoptosis-in-ovarian-cancer-cells-via-p38-mapk-jnk-signaling-pathway
#13
Jie Zhu, Ya Zheng, Haiyan Zhang, Hong Sun
Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a first-line treatment for type 2 diabetes mellitus, exerts anti-cancer and anti-proliferative action. 2-deoxyglucose (2-DG), a glucose analog, works as a competitive inhibitor of glycolysis. In this study, we show for the first time that metformin in combination with 2-DG inhibited growth, migration, invasion and induced cell cycle arrest of ovarian cancer cells in vitro. Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902459/anti-tumor-activity-of-metformin-from-metabolic-and-epigenetic-perspectives
#14
REVIEW
Xilan Yu, Wuxiang Mao, Yansheng Zhai, Chong Tong, Min Liu, Lixin Ma, Xiaolan Yu, Shanshan Li
Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27900046/proliferation-and-metastatic-potential-of-endometrial-cancer-cells-in-response-to-metformin-treatment-in-a-high-versus-normal-glucose-environment
#15
Amanda de Barros Machado, Vania Dos Reis, Sebastian Weber, Julia Jauckus, Ilma Simoni Brum, Helena von Eye Corleta, Thomas Strowitzki, Edison Capp, Ariane Germeyer
In order to improve our understanding of the potential preventive and therapeutic role of metformin, the present study aimed to investigate the capability of low-dose metformin in the efficient inhibition of cancer development and the reduction of the metastasis of endometrial adenocarcinoma type I and primary endometrial epithelial cells (eEPs), with the drug acting as a treatment in a hyperinsulinemic environment exposed to high and normal glucose conditions. The Ishikawa endometrial adenocarcinoma cell line and primary eEPs were exposed to an environment with high (17 mM) or normal glucose (5 mM) and treated with insulin, low-dose metformin (0...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27845068/combination-of-metformin-and-vsl-3-additively-suppresses-western-style-diet-induced-colon-cancer-in-mice
#16
Eun-Ju Chung, Eun-Ju Do, Sang-Yeob Kim, Eun A Cho, Dong-Hee Kim, Sehyung Pak, Sung Wook Hwang, Hyo Jeong Lee, Jeong-Sik Byeon, Byong Duk Ye, Dong Hoon Yang, Sang Hyoung Park, Suk-Kyun Yang, Jin-Ho Kim, Seung-Jae Myung
Western-style diet (WD) and dysbiosis are known to be associated with colonic inflammation, which contributes to carcinogenesis. Metformin (Met) exerts anti-inflammatory effects to induce AMP-activated protein kinase (AMPK), resulting in suppressed protein synthesis and reduced cell proliferation. Probiotic VSL#3 (V) modifies microbial composition. We investigated the chemopreventive mechanisms of Met and V in WD-induced colitis-associated colon carcinogenesis. Male BALB/c mice were randomly divided into five groups: a control diet (CD) group, WD group, WD+ Met (250mg/kg/day) group, WD+V (1...
January 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27814614/metformin-suppresses-crc-growth-by-inducing-apoptosis-via-adora1
#17
Bin Lan, Jian Zhang, Peng Zhang, Weihong Zhang, Shugang Yang, Dong Lu, Wenqin Li, Qinbao Dai
Accumulating evidence suggests that the anti-diabetic drug, metformin, exerts anti-proliferative effects in many types of cancers. However, the function and mechanisms of metformin in human colorectal cancer (CRC) remain unknown. Here, we show that metformin induces growth inhibition and apoptosis through activating AMPK-mTOR pathway in human colorectal cancer cells. Notably, metformin treatment significantly up-regulated adenosine A1 receptor (ADORA1) expression in human colorectal cancer cells, while suppression of ADORA1 activity by its specific inhibitor rescued the growth inhibition induced by metformin...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27793936/impact-of-h3k27-demethylase-inhibitor-gskj4-on-nsclc-cells-alone-and-in-combination-with-metformin
#18
Hikaru Watarai, Masashi Okada, Kenta Kuramoto, Hiroyuki Takeda, Hirotsugu Sakaki, Shuhei Suzuki, Shizuka Seino, Hiroyuki Oizumi, Mitsuaki Sadahiro, Chifumi Kitanaka
BACKGROUND: GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC), remains unknown. MATERIALS AND METHODS: The effect of GSKJ4 on the growth of three NSCLC cell lines and normal lung fibroblasts was investigated using the WST-8, dye exclusion, and colony formation assays...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27791206/metformin-treatment-reduces-temozolomide-resistance-of-glioblastoma-cells
#19
Seung Ho Yang, Shenglan Li, Guangrong Lu, Haipeng Xue, Dong H Kim, Jay-Jiguang Zhu, Ying Liu
It has been reported that metformin acts synergistically with temozolomide (TMZ) to inhibit proliferation of glioma cells including glioblastoma multiforme (GBM). However, the molecular mechanism underlying how metformin exerts its anti-cancer effects remains elusive. We used a combined experimental and bioinformatics approach to identify genes and complex regulatory/signal transduction networks that are involved in restoring TMZ sensitivity of GBM cells after metformin treatment. First, we established TMZ resistant GBM cell lines and found that the resistant cells regained TMZ sensitivity after metformin treatment...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27770555/prospective-study-of-type-2-diabetes-mellitus-anti-diabetic-drugs-and-risk-of-prostate-cancer
#20
Christel Häggström, Mieke Van Hemelrijck, Björn Zethelius, David Robinson, Birgitta Grundmark, Lars Holmberg, Soffia Gudbjörnsdottir, Hans Garmo, Pär Stattin
Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders...
February 1, 2017: International Journal of Cancer. Journal International du Cancer
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