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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#1
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28193839/metformin-promotes-amp-activated-protein-kinase-independent-suppression-of-%C3%AE-np63%C3%AE-and-inhibits-cancer-cell-viability
#2
Yong Yi, Deshi Chen, Juan Ao, Shengnan Sun, Min Wu, Xiaorong Li, Johann Bergholz, Yujun Zhang, Zhi-Xiong Xiao
The blood-glucose modifier metformin is used to treat type II diabetes and has also been shown to possess anti-cancer activities. Recent studies indicate that glucose deprivation can greatly enhance metformin-mediated inhibition of cell viability, but the molecular mechanism involved in this inhibition is unclear. In this study, we report that under glucose deprivation metformin inhibited expression of ΔNp63α, a p53 family member involved in cell adhesion pathways, resulting in disruption of cell-matrix adhesion and in subsequent apoptosis in human squamous carcinoma cells...
February 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28193239/buformin-inhibits-the-stemness-of-erbb-2-overexpressing-breast-cancer-cells-and-premalignant-mammary-tissues-of-mmtv-erbb-2-transgenic-mice
#3
Amanda B Parris, Qingxia Zhao, Erin W Howard, Ming Zhao, Zhikun Ma, Xiaohe Yang
BACKGROUND: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28182659/metformin-exhibits-preventive-and-therapeutic-efficacy-against-experimental-cystic-echinococcosis
#4
Julia A Loos, Valeria A Dávila, Christian R Rodrígues, Romina Petrigh, Jorge A Zoppi, Fernando A Crocenzi, Andrea C Cumino
Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28161619/combination-of-metformin-with-chemotherapeutic-drugs-via-different-molecular-mechanisms
#5
REVIEW
Mei Peng, Kwame Oteng Darko, Ting Tao, Yanjun Huang, Qiongli Su, Caimei He, Tao Yin, Zhaoqian Liu, Xiaoping Yang
Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits...
January 23, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28157701/metformin-treated-cancer-cells-modulate-macrophage-polarization-through-ampk-nf-%C3%AE%C2%BAb-signaling
#6
Chi-Fu Chiang, Ting-Ting Chao, Yu-Fu Su, Chia-Chen Hsu, Chu-Yen Chien, Kuo-Chou Chiu, Shine-Gwo Shiah, Chien-Hsing Lee, Shyun-Yeu Liu, Yi-Shing Shieh
Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28128472/effects-on-energy-metabolism-of-two-guanidine-molecules-boc-2-creatine-and-metformin
#7
Patrizia Garbati, Silvia Ravera, Sonia Scarfì, Annalisa Salis, Camillo Rosano, Alessandro Poggi, Gianluca Damonte, Enrico Millo, Maurizio Balestrino
Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism...
January 27, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28122334/metformin-a-metabolic-modulator
#8
Federico Pietrocola, Guido Kroemer
Recent findings have shed new light on the mechanisms of action through which biguanides exert their anti-aging and cytostatic effects in Caenorhabditis elegans and human cell lines. The drop in energy charge resulting from the metformin mediated inhibition of mitochondrial activity affects the function of the nuclear pore complex, blocks mTOR signaling and enhances the expression of ACAD10. Whether the inhibition of this pathway is truly responsible for the anti-diabetic and cancer effects of the drug in mammals remains to be established...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28114390/high-glucose-mediated-stat3-activation-in-endometrial-cancer-is-inhibited-by-metformin-therapeutic-implications-for-endometrial-cancer
#9
John J Wallbillich, Srirama Josyula, Uksha Saini, Roman A Zingarelli, Kalpana Deepa Priya Dorayappan, Maria K Riley, Ross A Wanner, David E Cohn, Karuppaiyah Selvendiran
OBJECTIVES: STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. METHODS: In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR)...
2017: PloS One
https://www.readbyqxmd.com/read/28104298/kr%C3%A3-pple-like-factor-10-regulates-radio-sensitivity-of-pancreatic-cancer-via-uv-radiation-resistance-associated-gene
#10
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28103701/metformin-prevents-the-progression-of-dysplastic-mucosa-of-the-head-and-neck-to-carcinoma-in-nondiabetic-patients
#11
Michael Zvi Lerner, Niv Mor, Hyung Paek, Andrew Blitzer, Marshall Strome
OBJECTIVE: Metformin is an oral anti-hyperglycemic agent used to treat type 2 diabetes mellitus (DM). In vitro and animal models have shown that metformin can prevent the progression of oral lesions to carcinoma; however, there is conflicting data in the clinical literature regarding risk reduction for malignancy in head and neck cancer (HNC). STUDY DESIGN: Case series. METHODS: We present 3 cases in which adjuvant metformin therapy was used to treat recurrent and multifocal dysplastic lesions in previously treated nondiabetic HNC patients...
January 1, 2017: Annals of Otology, Rhinology, and Laryngology
https://www.readbyqxmd.com/read/28088698/metformin-enhancing-the-antitumor-efficacy-of-carboplatin-against-ehrlich-solid-carcinoma-grown-in-diabetic-mice-effect-on-igf-1-and-tumoral-expression-of-igf-1-receptors
#12
Dina M Abo-Elmatty, Eman A Ahmed, Mona K Tawfik, Seham A Helmy
Diabetes has been listed as a risk factor for various types of cancer. Cancer cell development can be promoted by increased levels of IGF-1 and hyperinsulinemia that are associated with diabetes type II. Metformin is an anti-diabetic agent and its potential antitumor impact has become the objective of numerous studies. In this vein, we hypothesize that using metformin in diabetes type II mice may synergistic with carboplatin for reducing the risk of cancer. Therefore, the study aimed to evaluate the in vivo antitumor activity of metformin against solid EAC tumor growth in female diabetic mice and its potential pro-apoptotic and anti-proliferative effects with clarification of its inconclusive biological mechanisms...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28052934/fixed-dose-combinations-of-pioglitazone-and-metformin-for-lung-cancer-prevention
#13
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 is 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 benzo[a]pyrene (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
#14
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
#15
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
#16
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...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#17
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
#18
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...
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
#19
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
#20
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
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