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Metformin cancer

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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
#1
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/27903154/type-2-diabetes-mellitus-and-cancer-the-role-of-pharmacotherapy
#2
Gadi Shlomai, Brian Neel, Derek LeRoith, Emily Jane Gallagher
Purpose Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. Design This study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27903152/obesity-and-cancer-mechanisms-cancer-metabolism
#3
Benjamin D Hopkins, Marcus D Goncalves, Lewis C Cantley
Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. The positive energy balance linked with obesity induces a variety of systemic changes including altered levels of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines. Each of these factors alters the nutritional milieu and has the potential to create an environment that favors tumor initiation and progression. Although the complete ramifications of obesity as it relates to cancer are still unclear, there is convincing evidence that reducing the magnitude of the systemic hormonal and inflammatory changes has significant clinical benefits...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27903149/obesity-and-breast-cancer-prognosis-evidence-challenges-and-opportunities
#4
Sao Jiralerspong, Pamela J Goodwin
Purpose To summarize the evidence of an association between obesity and breast cancer prognosis. Methods We reviewed the literature regarding overweight and obesity and breast cancer survival outcomes, overall and with regard to breast cancer subtypes, breast cancer therapies, biologic mechanisms, and possible interventions. We summarize our findings and provide clinical management recommendations. Results Obesity is associated with a 35% to 40% increased risk of breast cancer recurrence and death and therefore poorer survival outcomes...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902459/anti-tumor-activity-of-metformin-from-metabolic-and-epigenetic-perspectives
#5
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
#6
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/27890326/the-effect-of-metabolic-comorbidities-and-commonly-used-drugs-on-the-prognosis-of-patients-with-ovarian-cancer
#7
Daniel Bar, Ofer Lavie, Nili Stein, Ido Feferkorn, Ayelet Shai
BACKGROUND: Diabetes mellitus is associated with an increased risk of recurrence in patients with ovarian cancer. Retrospective studies suggested that the use of statins, metformin and beta blockers is associated with improved prognosis in these patients. Patients with diabetes often suffer from hypertension and are usually treated concomitantly by several classes of drugs. Our aim was to assess the independent contribution of diabetes mellitus and hypertension and of the use of aspirin, statins, metformin and beta blockers on the risk of ovarian cancer recurrence and mortality...
October 14, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27881709/relationship-between-metformin-use-and-recurrence-and-survival-in-patients-with-resected-stage-iii-colon-cancer-receiving-adjuvant-chemotherapy-results-from-north-central-cancer-treatment-group-n0147-alliance
#8
Preet Paul Singh, Qian Shi, Nathan R Foster, Axel Grothey, Suresh G Nair, Emily Chan, Anthony F Shields, Richard M Goldberg, Sharlene Gill, Morton S Kahlenberg, Frank A Sinicrope, Daniel J Sargent, Steven R Alberts
BACKGROUND: Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. PATIENTS AND METHODS: Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use...
November 23, 2016: Oncologist
https://www.readbyqxmd.com/read/27875520/the-cell-autonomous-mechanisms-underlying-the-activity-of-metformin-as-an-anticancer-drug
#9
Francesca Sacco, Alberto Calderone, Luisa Castagnoli, Gianni Cesareni
The biguanide drug metformin profoundly affects cell metabolism, causing an impairment of the cell energy balance and triggering a plethora of pleiotropic effects that vary depending on the cellular or environmental context. Interestingly, a decade ago, it was observed that metformin-treated diabetic patients have a significantly lower cancer risk. Although a variety of in vivo and in vitro observations emphasising the role of metformin as anticancer drug have been reported, the underlying mechanisms are still poorly understood...
November 22, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27870711/the-effect-of-metformin-on-oncological-outcomes-in-patients-with-cervical-cancer-with-type-2-diabetes-mellitus
#10
Jitti Hanprasertpong, Ingporn Jiamset, Alan Geater, Thanarpan Peerawong, Wikanda Hemman, Sasima Kornsilp
OBJECTIVE: The aim of this study was to evaluate any association between metformin use and oncological outcomes of cervical cancer in patients with type 2 diabetes mellitus (DM). METHODS: We retrospectively identified 248 patients with cervical cancer with type 2 DM who received primary treatment between 2004 and 2015. The clinicopathological characteristics and oncological outcomes were collected and analyzed. The patients were then separated into metformin use (n = 118) or non-metformin use (n = 130) groups...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27869650/inhibiting-mitochondrial-respiration-prevents-cancer-in-a-mouse-model-of-li-fraumeni-syndrome
#11
Ping-Yuan Wang, Jie Li, Farzana L Walcott, Ju-Gyeong Kang, Matthew F Starost, S Lalith Talagala, Jie Zhuang, Ji-Hoon Park, Rebecca D Huffstutler, Christina M Bryla, Phuong L Mai, Michael Pollak, Christina M Annunziata, Sharon A Savage, Antonio Tito Fojo, Paul M Hwang
Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism in patients. However, the implications of altered mitochondrial function for tumorigenesis in LFS are unclear. Here, we have reported that genetic or pharmacologic disruption of mitochondrial respiration improves cancer-free survival in a mouse model of LFS that expresses mutant p53. Mechanistically, inhibition of mitochondrial function increased autophagy and decreased the aberrant proliferation signaling caused by mutant p53...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27861855/effect-of-statin-on-hepatocellular-carcinoma-in-patients-with-type-2-diabetes-a-nationwide-nested-case-control-study
#12
Gyuri Kim, Suk-Yong Jang, Eugene Han, Yong-Ho Lee, Se-Young Park, Chung Mo Nam, Eun Seok Kang
Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio...
November 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27861146/metformin-and-esophageal-cancer-risk-in-taiwanese-patients-with-type-2-diabetes-mellitus
#13
Chin-Hsiao Tseng
This study evaluated whether metformin might reduce esophageal cancer risk. Patients with type 2 diabetes mellitus diagnosed during 1999-2005 were recruited from the reimbursement database of Taiwan's National Health Insurance. Those newly treated with metformin (n = 288013, "ever users of metformin") or other antidiabetic drugs (n = 16216, "never users of metformin") were followed until December 31, 2011. Sensitivity analyses were conducted in a matched-pair sample of 16216 never users and 16216 ever users...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#14
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27845068/combination-of-metformin-and-vsl-3-additively-suppresses-western-style-diet-induced-colon-cancer-in-mice
#15
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...
November 12, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27836248/a-review-for-clinicians-prostate-cancer-and-the-antineoplastic-properties-of-metformin
#16
REVIEW
Stephen J Hankinson, Mina Fam, Nitin N Patel
OBJECTIVES: Metformin has numerous antineoplastic effects including an AMP-activated protein kinase-dependent mechanism, AMP-activated protein kinase-independent mechanisms, alteration of insulin and insulin-like growth factor signaling pathways, and suppression of androgen signaling pathways that trigger prostate cancer growth and proliferation. In contrast to other malignancies that are associated with increased incidence among patients with obesity and type II diabetes mellitus (T2DM), epidemiological studies suggest that obesity and T2DM may impart a protective effect on prostate cancer incidence by creating a set of metabolic conditions that lower androgen levels...
November 8, 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27830724/activation-of-ampk%C3%AE-mediates-additive-effects-of-solamargine-and-metformin-on-suppressing-muc1-expression-in-castration-resistant-prostate-cancer-cells
#17
SongTao Xiang, QiuHong Zhang, Qing Tang, Fang Zheng, JingJing Wu, LiJun Yang, Swei Sunny Hann
Prostate cancer is the second most common cause of cancer-related deaths worldwide. The mucin 1 (MUC1) oncoprotein is highly expressed in human prostate cancers with aggressive features. However, the role for MUC1 in occurrence and progression of castration-resistant prostate cancer (CRPC) remained elusive. In this study, we showed that solamargine, a major steroidal alkaloid glycoside, inhibited the growth of CRPC cells, which was enhanced in the presence of metformin. Furthermore, we found that solamargine increased phosphorylation of AMPKα, whereas reducing the protein expression and promoter activity of MUC1...
November 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27825799/combination-of-2-deoxy-d-glucose-and-metformin-for-synergistic-inhibition-of-non-small-cell-lung-cancer-a-reactive-oxygen-species-and-p-p38-mediated-mechanism
#18
Xiao-Bin Hou, Ting-Hui Li, Zhi-Peng Ren, Yang Liu
Targeting metabolism of lung cancer cells is a promising methodology for the treatment of lung cancer. In this regard, 2-Deoxy d-glucose (2-dDG) has been reported to inhibit cell proliferation by intervening the glycolytic pathway. However, phase I clinical trial of 2-dDG demonstrated cardiac side effects at higher dosage. Metformin (Met), on the other hand, has been reported to improve pathological response to chemotherapy in non-small cell lung cancer (NSCLC) patients. In this study, we propose that combination therapy of 2-dDG with Met will demonstrate enhanced cytotoxicity than either compound alone...
November 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27814614/metformin-suppresses-crc-growth-by-inducing-apoptosis-via-adora1
#19
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/27802188/metformin-enhances-the-radiosensitivity-of-human-liver-cancer-cells-to-%C3%AE-rays-and-carbon-ion-beams
#20
Eun Ho Kim, Mi-Sook Kim, Yoshiya Furusawa, Akiko Uzawa, Soorim Han, Won-Gyun Jung, Sei Sai
The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt...
October 27, 2016: Oncotarget
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