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Metformin anti-cancer

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https://www.readbyqxmd.com/read/28822889/metformin-targets-gastric-cancer-stem-cells
#1
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...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#2
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819370/metformin-inhibits-gemcitabine-induced-apoptosis-in-pancreatic-cancer-cell-lines
#3
Dietmar Zechner, Ann-Christin Albert, Florian Bürtin, Brigitte Vollmar
Many preclinical and clinical studies are currently evaluating metformin in combination with classical therapeutic agents as anti-cancer therapy. In this study we used three distinct pancreatic cancer cell lines and evaluated cell death by trypan blue assay and Western Blots using antibodies directed against cleaved caspase 3 and PARP. Surprisingly, we observed that 20mM metformin did not enhance, but rather inhibited gemcitabine induced cell death in murine 7265PDA, 6606PDA and 6606l cells. Microenvironmental aspects such as oxygen supply or the pH value did not influence the inhibition of cancer cell apoptosis by metformin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28802253/the-combination-of-metformin-and-valproic-acid-induces-synergistic-apoptosis-in-the-presence-of-p53-and-androgen-signaling-in-prostate-cancer
#4
Linh N K Tran, Ganessan Kichenadasse, Lisa M Butler, Margaret M Centenera, Katherine L Morel, Rebecca J Ormsby, Michael Z Michael, Karen M Lower, Pamela J Sykes
We investigated the potential of combining the hypoglycemic drug metformin (MET) and the anti-epileptic drug valproic acid (VPA), which act via different biochemical pathways, to provide enhanced anti-tumor responses in prostate cancer. Prostate cancer cell lines (LNCaP and PC-3), normal prostate epithelial cells (PrEC), and patient-derived prostate tumor explants were treated with MET and/or VPA. Proliferation and apoptosis were assessed. The role of p53 in response to MET+VPA was assessed in cell lines using RNA interference in LNCaP (p53(+)) and ectopic expression of p53 in PC-3 (p53(-))...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28802138/inhibition-of-bioenergetic-metabolism-by-the-combination-of-metformin-and-2-deoxyglucose-highly-decreases-viability-of-feline-mammary-carcinoma-cells
#5
María Florencia Arbe, Chiara Fondello, Lucrecia Agnetti, Gabriel Martín Álvarez, Matías Nicolás Tellado, Gerardo Claudio Glikin, Liliana María Elena Finocchiaro, Marcela Solange Villaverde
Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3+) and Ki67<5%) and AlRATN (HER2 (-) and Ki67>15%)...
August 3, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28801373/metformin-and-melatonin-in-adrenocortical-carcinoma-morphoproteomics-and-biomedical-analytics-provide-proof-of-concept-in-a-case-study
#6
Robert E Brown, Jamie Buryanek, Mary F McGuire
Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli's recent preclinical studies that 1. "in vitro" metformin modulates the ACC cell model H295R and 2. "in vivo" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli's studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung...
August 2017: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/28769006/mechanistic-study-of-inhibitory-effects-of-metformin-and-atorvastatin-in-combination-on-prostate-cancer-cells-in-vitro-and-in-vivo
#7
Zhen-Shi Wang, Hua-Rong Huang, Lan-Yue Zhang, Seungkee Kim, Yan He, Dong-Li Li, Chelsea Farischon, Kun Zhang, Xi Zheng, Zhi-Yun Du, Susan Goodin
Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#8
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28742810/effect-of-calcium-electroporation-in-combination-with-metformin-in-vivo-and-correlation-between-viability-and-intracellular-atp-level-after-calcium-electroporation-in-vitro
#9
Stine Krog Frandsen, Julie Gehl
BACKGROUND: Calcium electroporation is a new experimental anti-cancer treatment where calcium is internalized into cells by application of short, high voltage pulses. Calcium electroporation has been shown to induce tumor necrosis associated with ATP depletion while the effect on normal fibroblasts was limited when investigated in a 3D in vitro spheroid model. We aimed to investigate the effect of calcium electroporation in combination with metformin, a drug that affects intracellular ATP level...
2017: PloS One
https://www.readbyqxmd.com/read/28736111/metformin-therapy-reduces-the-risk-of-malignancy-after-heart-transplantation
#10
Yael Peled, Jacob Lavee, Eugenia Raichlin, Moshe Katz, Michael Arad, Yigal Kassif, Amir Peled, Elad Asher, Dan Elian, Yedael Har-Zahav, Nir Shlomo, Dov Freimark, Ilan Goldenberg, Robert Klempfner
BACKGROUND: Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. METHODS: The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up...
June 23, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28732480/metformin-and-longevity-metal-a-window-of-opportunity-study-investigating-the-biological-effects-of-metformin-in-localised-prostate-cancer
#11
Danielle Crawley, Ashish Chandra, Massimo Loda, Cheryl Gillett, Paul Cathcart, Ben Challacombe, Gary Cook, Declan Cahill, Aida Santa Olalla, Fidelma Cahill, Gincy George, Sarah Rudman, Mieke Van Hemelrijck
BACKGROUND: Metformin is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to its anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumours, including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor - 1 (IGF-1) levels play a role in PCa development and progression...
July 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28723636/redox-dependent-modulation-of-metformin-contributes-to-enhanced-sensitivity-of-esophageal-squamous-cell-carcinoma-to-cisplatin
#12
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...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#13
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#14
Hyun-Soo Shin, Jiyeon Ko, Dal-Ah Kim, Eun-Sun Ryu, Hye-Myung Ryu, Sun-Hee Park, Yong-Lim Kim, Eok-Soo Oh, Duk-Hee Kang
Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT). We investigated the effect of metformin on EMT of human peritoneal mesothelial cells (HPMC) and animal model of peritoneal dialysis (PD). TGF-β1-induced EMT in HPMC was ameliorated by metformin...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28703040/metformin-adjunct-therapy-in-cancer-treatment
#15
Ann R Lurati
An employee undergoing cancer treatment was prescribed metformin, a medication used in the treatment of type 2 diabetes and currently used as adjunct therapy for cancer. Metformin's anti-inflammatory properties inhibit tumor growth. It is speculated that cancer cells develop a metabolism that enhances aerobic glycolysis, which promotes cell growth and increases the need for glucose. Metformin decreases insulin in the blood, which decreases the amount of glucose available to cancer cells, thus starving the cells of nutrition, resulting in cell death...
July 1, 2017: Workplace Health & Safety
https://www.readbyqxmd.com/read/28669771/antidiabetic-antioxidant-and-anti-inflammatory-properties-of-water-and-n-butanol-soluble-extracts-from-saharian-anvillea-radiata-in-high-fat-diet-fed-mice
#16
Chouaib Kandouli, Mathieu Cassien, Anne Mercier, Caroline Delehedde, Emilie Ricquebourg, Pierre Stocker, Mourad Mekaouche, Zineb Leulmi, Aicha Mechakra, Sophie Thétiot-Laurent, Marcel Culcasi, Sylvia Pietri
ETHNOPHARMACOLOGICAL RELEVANCE: According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. AIM OF THE STUDY: To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties...
July 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28651817/angiogenesis-and-cancer-stem-cells-new-perspectives-on-therapy-of-ovarian-cancer
#17
REVIEW
Anna Markowska, Stefan Sajdak, Janina Markowska, Adam Huczyński
Failure in ovarian cancer therapy, following cytoreduction and chemotherapy, is related to the presence of cancer stem cells - a small subpopulation of cells resistant to chemotherapy and irradiation - in the tumour which may cause cancer relapse and manifestation of metastases. Therapies targeted at Cancer Stem Cells (CSCs), such as those employing metformin (a drug used in the treatment of diabetes type II) and salinomycin, an antibiotic isolated from Streptococcus albus bacteria, seem promising. Anti-angiogenic therapy with bevacizumab was found to be effective in all phases of ovarian cancer treatment...
June 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#18
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28641310/potentiating-the-effects-of-radiotherapy-in-rectal-cancer-the-role-of-aspirin-statins-and-metformin-as-adjuncts-to-therapy
#19
K J Gash, A C Chambers, D E Cotton, A C Williams, M G Thomas
BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included...
July 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28640441/adipose-tissue-derived-omentin-1-function-and-regulation
#20
Takuya Watanabe, Kaho Watanabe-Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe
Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin-1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor-21 and dexamethasone. Several lines of experimental evidence have shown that omentin-1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti-inflammatory, anti-atherosclerotic, and cardiovascular protective effects via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) signaling...
June 18, 2017: Comprehensive Physiology
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