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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28319830/anti-proliferative-effect-of-metformin-on-a-feline-injection-site-sarcoma-cell-line-independent-of-mtor-inhibition
#1
J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28274936/no-decreased-risk-of-gastrointestinal-cancers-in-users-of-metformin-in-the-netherlands-a-time-varying-analysis-of-metformin-exposure
#2
Roy G de Jong, Andrea M Burden, Sander de Kort, Myrthe van Herk-Sukel, Pauline A Vissers, Paddy K Janssen, Harm R Haak, Ad A M Masclee, Frank de Vries, Maryska L Janssen-Heijnen
Previous studies on metformin use and gastrointestinal (GI) cancer risk have yielded inconclusive results on metformin's chemoprotective effects. We aimed to evaluate GI cancer risk in users of metformin in The Netherlands using a time-varying approach in a large population-based database. A cohort study was performed using the NCR-PHARMO database. Patients using ≥1 non-insulin anti-diabetic drug (NIAD) during 1998-2011 were included (N=57,621). Exposure to NIADs was modelled time-varyingly. Cox regression analysis estimated hazard ratios (HRs) of GI cancers in current metformin users versus current users of other NIADs...
March 8, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28274796/dual-functional-lipomet-mediates-envelope-type-nanoparticles-to-combinational-oncogene-silencing-and-tumor-growth-inhibition
#3
Kai Shi, Yi Zhao, Lei Miao, Andrew Satterlee, Matthew Haynes, Cong Luo, Sara Musetti, Leaf Huang
The success of small interfering RNA (siRNA)-mediated gene silencing for cancer therapy is still limited because of its instability and poor intracellular internalization. Traditional cationic carriers cannot adequately meet the need for clinical application of siRNA. We herein report a dual-functional liposome containing a cholesterol derivative of metformin, i.e., LipoMET, which takes advantage of the fusogenic activity as well as intrinsic tumor apoptosis inducing ability of biguanide moiety to achieve a combinational anti-oncogenic effect...
March 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#4
Samson Mathews Samuel, Suparna Ghosh, Yasser Majeed, Gnanapragasam Arunachalam, Mohamed M Emara, Hong Ding, Chris R Triggle
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose...
March 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28260041/metformin-suppresses-the-expression-of-sonic-hedgehog-in-gastric-cancer-cells
#5
Zhou Song, Bo Wei, Canrong Lu, Xiaohui Huang, Peiyu Li, Lin Chen
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC‑27 and MKN‑45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma‑associated oncogene (Gli)‑1, Gli‑2 and Gli‑3 were examined using western blot and reverse transcription‑quantitative polymerase chain reaction analyses...
February 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258677/metformin-its-potential-anti-cancer-and-anti-aging-effects
#6
Monika Podhorecka, Blanca Ibanez, Anna Dmoszyńska
The generally accepted mechanism of metformin's effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin's beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28252027/combining-metformin-and-nelfinavir-exhibits-synergistic-effects-against-the-growth-of-human-cervical-cancer-cells-and-xenograft-in-nude-mice
#7
Chenglai Xia, Ruihong Chen, Jinman Chen, Qianqian Qi, Yanbin Pan, Lanying Du, Guohong Xiao, Shibo Jiang
Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241849/metformin-potentiates-the-effect-of-arsenic-trioxide-suppressing-intrahepatic-cholangiocarcinoma-roles-of-p38-mapk-erk3-and-mtorc1
#8
Sunbin Ling, Haiyang Xie, Fan Yang, Qiaonan Shan, Haojiang Dai, Jianyong Zhuo, Xuyong Wei, Penghong Song, Lin Zhou, Xiao Xu, Shusen Zheng
BACKGROUND: Arsenic trioxide (ATO) is commonly used in the treatment of acute promyelocytic leukemia (APL), but does not benefit patients with solid tumors. When combined with other agents or radiation, ATO showed treatment benefits with manageable toxicity. Previously, we reported that metformin amplified the inhibitory effect of ATO on intrahepatic cholangiocarcinoma (ICC) cells more significantly than other agents. Here, we investigated the chemotherapeutic sensitization effect of metformin in ATO-based treatment in ICC in vitro and in vivo and explored the underlying mechanisms...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#9
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#10
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
#11
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
#12
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
#13
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
#14
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...
March 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
April 2017: Annals of Otology, Rhinology, and Laryngology
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