Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

Yu, Xilan; Mao, Weihua; Zhai, Yansheng; Tong, Chong Wai; Liu, Min; Ma, Lixin; Yu, Xiaohui; Li, Shanshan

doi:10.18632/oncotarget.13639

Cited by 69 publications

(55 citation statements)

References 59 publications

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“…In the past decade, many epidemiological studies showed the association between metformin use and the reduced risk and improved survival of patients with several types of cancers, including gynecological cancers. The beneficial effects of metformin use on EC may depend on common anticancer mechanisms present in other gynecological cancers [33] and even all tumors [34], but the exact molecular mechanism has not yet been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Tang

Zhu

et al. 2017

BioMed Research International

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Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients.

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Section: Discussionmentioning

confidence: 99%

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Tang

Zhu

et al. 2017

BioMed Research International

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“…While aerobic glycolysis is a known feature of cancer cells, targeting this pathway for therapy has proven challenging due to the cytotoxicity of many anti-glycolytic agents [25]. Biguanides, such as metformin and phenformin, are common therapeutics for the treatment of type 2 diabetes, and have recently been reported to exhibit anticancer activity in vitro and in vivo [26][27][28]. Specifically, both agents have an inhibitory effect on glycolysis and oxidative metabolism.…”

Section: Discussionmentioning

confidence: 99%

Loss of Rb1 Enhances Glycolytic Metabolism in Kras-Driven Lung Tumors In Vivo

Conroy

Dougherty

Kruer

et al. 2020

Cancers

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Dysregulated metabolism is a hallmark of cancer cells and is driven in part by specific genetic alterations in various oncogenes or tumor suppressors. The retinoblastoma protein (pRb) is a tumor suppressor that canonically regulates cell cycle progression; however, recent studies have highlighted a functional role for pRb in controlling cellular metabolism. Here, we report that loss of the gene encoding pRb (Rb1) in a transgenic mutant Kras-driven model of lung cancer results in metabolic reprogramming. Our tracer studies using bolus dosing of [U-13C]-glucose revealed an increase in glucose carbon incorporation into select glycolytic intermediates. Consistent with this result, Rb1-depleted tumors exhibited increased expression of key glycolytic enzymes. Interestingly, loss of Rb1 did not alter mitochondrial pyruvate oxidation compared to lung tumors with intact Rb1. Additional tracer studies using [U-13C,15N]-glutamine and [U-13C]-lactate demonstrated that loss of Rb1 did not alter glutaminolysis or utilization of circulating lactate within the tricarboxylic acid cycle (TCA) in vivo. Taken together, these data suggest that the loss of Rb1 promotes a glycolytic phenotype, while not altering pyruvate oxidative metabolism or glutamine anaplerosis in Kras-driven lung tumors.

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“…In a recent review based on 179 trials and 25 observational studies, the use of metformin as monotherapy or in combination as first-line treatment of hyperglycemia has been strongly recommended, given its relative safety and beneficial effects on hemoglobin A1c, weight, and cardiovascular mortality (compared with sulfonylureas) (28). Furthermore, metformin has been extensively studied to suppress tumorigenesis by direct and indirect mechanisms (29).…”

Section: How Do We Manage Hyperglycemia In Diabetic Patient With Ckd?mentioning

confidence: 99%

Antidiabetic Medication in Patients with Chronic Kidney Disease: What's New?

Dominijanni

Cipriani

Malaguti

et al. 2017

Nephrology @ Point of Care

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QUESTIONS @ POINT OF CARE an initial damage with rare microaneurysm and intraretinal hemorrhages, without edema or exudates. The echocardiogram showed normal values for the whole cardiac measurement except for the initial left ventricular hypertrophy (LVH), with a normal result of 60% for the left ventricular ejection fraction (LVEF) and without valvular abnormalities. Finally, the results of the arterial venous Doppler ultrasound examination of the neck and lower limbs and of the upper and lower limbs electromyography (EMG) were normal. The glycemic parameters were kept under control with metformin 1000 mg twice a day. The patient was a nonsmoker, not addicted to alcohol, but his overweight suggested that a prompt lifestyle change was mandatory. He started taking omega-3 (1000 mg twice a day) and a combination of ezetimibe-simvastatin 10/20 mg once a day. What do we know about diabetic nephropathy and its natural history? The incidence and prevalence of type 2 diabetes mellitus (T2DM) will continue to increase and it's widely recognized that the number of adults with diabetes worldwide will rise from 382 million in 2013 to 592 million in 2035, especially in developing countries (1). Diabetic nephropathy (DN) is one of the most frequent microvascular complications of diabetes. Whereas in the USA has been estimated that 50% of prevalent patients under dialysis are affected by diabetes (2), in Italy the prevalence of diabetic patients on dialysis has been estimated at 25.3% (3). Fortunately, only one-third of patients with T2DM experience DN (4). According to medical literature, diabetes leads to significant renal abnormalities in a period of approximately 20 years and the reduction in estimated glomerular filtration

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Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

Cited by 69 publications

References 59 publications

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

Loss of Rb1 Enhances Glycolytic Metabolism in Kras-Driven Lung Tumors In Vivo

Antidiabetic Medication in Patients with Chronic Kidney Disease: What's New?

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