Metformin: A Possible Option in Cancer Chemotherapy (original) (raw)
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Metformin: Possible Use of a Diabetes Drug in Treatment of Cancer
Clinical research in diabetes and endocrinology, 2018
The biguanide drug metformin used for treating Type 2 diabetes has anticancer properties and affects many pathways involving glucose metabolism, energy balance, and cell survival. A number of retrospective clinical studies have indicated a reduced risk of cancer and improved cancer outcomes in Type 2 diabetic patients taking metformin. Several of its effects are mediated through the induction of cellular stress and subsequent activation of AMP kinase, but many other mechanisms act independently of AMP kinase activation. Metformin has been shown to inhibit the effects of tumor necrosis factor (TNF)-alpha. TNF-alpha interferes with insulin signaling to produce insulin resistance in the insulin signaling pathway and promotes apoptosis through NF-KB in the apoptosis pathway. In addition, metformin reduces cellular proliferation by decreasing the amount of available insulin or by directly affecting the mammalian target of rapamycin complex involved with regulating protein synthesis. It c...
An update on the effectiveness of metformin alone and with chemotherapy drugs on tumor cells
European Journal of Cell Science, 2020
Cancer and diabetes are critical risks that reveal many complications. Metformin has long been used in herbal medicine as an anti-diabetes medicine. It is one of the first-line therapies for type two (T2D that has gained use across different healthcare systems. It is the most preferred form of treatment due to its safety, being readily available, and widely used because it has fewer and affordable side effects for many users. The repurposing of metformin used in other treatments to treat cancer patients or the combination of targeted treatments with metformin can reduce the side effects of chemotherapy drugs, enhance the effectiveness, and may reduce resistance to targeted drugs. The mechanism of metformin has been demonstrated and its association with other drugs. It Inhibits cell growth and stops the cell cycle, and stimulates programmed cell death and autophagy of various cancer cells. Patients with diabetes and different kinds of malignancies such as colorectal, hepatic, and ova...
Metformin : A Future Anticancerous Drug
2019
Metformin is a generic drug, used for treatment of type 2 diabetes mellitus. Metformin is known to activate the AMPK pathway, lower the gluconeogenesis in hepatocytes and improves the insulin signaling in some target cells, thus exhibiting the anti-hyperglycemic activity. In case of diabetes the persistent hyperglycemia, hyperinsulinemia and oxidative stress may become a favorable condition for cancerous growth. Hence the people, suffering from diabetes are more prone to cancer. On the other side it has been observed that the chance of occurrence of cancer decreases in those diabetic patients, who regularly uptake Metformin. This indicates towards the anticancerous potential of Metformin. In last decade a large number of epidemiological studies suggested a strong protective effect of metformin against a number of cancers. A large number of studies exploring the antiproliferative potential of Metformin suggested that there is not common mechanism, rather in different types of cancer ...
Assessing the anticancer effects of metformin
F1000Research
Background: Metformin is an antihyperglycemic biguanide that is used as the first-line treatment for type 2 diabetes mellitus (T2DM). Metformin use helps control T2DM which is one of the many risk factors for cancer and is proposed to have multiple antagonistic actions against cancer cells. Metformin induces adenosine monophosphate-activated protein kinase (AMPK)-driven cascades, involving two pathways, a direct and an indirect one. This leads to a decrease in the mechanistic activity of mammalian target of rapamycin (mTOR), folate level, c-MYC (a family of regulator genes and proto-oncogenes), NF-κB (nuclear factor kappa of B cell), and also increases tumor suppressor P53 phosphorylation. These cascades will also decrease cyclin D1, reactive oxygen species (ROS), and increase mTOR complex1 (mTORC1) concentrations, apoptosis, and autophagy. Metformin also exerts anti-inflammatory effects through reducing interleukins 6 (IL6) and 8 (IL8), inhibition of protein translation via LKB1 (l...
Paper of metformin and breast cancer
Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Cotreatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.
Metformin in Cancer Prevention and Therapy: New Application of an Old Drug
Journal of Medical Science And clinical Research, 2017
Metformin, one of most widely prescribed oral anti-diabetic drug has emerged as a potential anti-cancer drug because of its potential anti-tumorigenic effects that are thought to be independent of its hypoglycaemic effects. Over the last few years, a mass of epidemiologic, outcomes and preclinical data has emerged that demonstrate the potential clinical relevance and the mechanistic basis of the anti-cancer activity of this well tolerated drug. Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: activation of LKB1/AMPK pathway, induction of cell cycle arrest and/or apoptosis, inhibition of protein synthesis, reduction in circulating insulin levels, inhibition of the unfolded protein response (UPR), activation of the immune system, and eradication of cancer stem cells. There is also a growing number of evidence, mostly in the form of retrospective clinical studies that suggest that metformin may be associated with a decreased risk of developing cancer and with a better response to chemotherapy. There are currently several ongoing randomized clinical trials that incorporate metformin as an adjuvant to classic chemotherapy and aim to evaluate its potential benefits in this setting. This review highlights basic aspects of the molecular biology of metformin and summarizes new advances in basic science as well as intriguing results from recent clinical studies.
Journal of clinical medicine research, 2017
Metformin has been proven to be one of the most safe and effective antihyperglycemic agents. Through more than six decades of metformin use, it became the most studied hypoglycemic agent; through these studies, it showed a marvelous non-glycemic related effect. These effects include modulation of different points of cancer timeline, weight reduction, cardiovascular health, thyroid diseases, polycystic ovaries disease and many other medical conditions. The aim of this review was to assess the effect of metformin on non-diabetes related medical diseases. We have examined the studies published in PubMed and summarized different randomized controlled trials, observational trials and review articles. This review has summarized most of the non-glycemic effects of metformin. Metformin has been solidly shown to be effective in weight control with certain medications, effective in neuroprotection, in endothelial health, in control of anti-HIV agent side effects and many other crucial health ...
Metformin: Its emerging role in oncology
HORMONES, 2011
Metformin is considered, in conjunction with lifestyle modification, as a first-line treatment modality for type 2 diabetes mellitus (DM). recently, several clinical studies have reported reduced incidence of neoplastic diseases in DM type 2 patients treated with metformin, as compared to diet or other antidiabetic agents. Moreover, in vitro studies have disclosed significant antiproliferative and proapoptotic effects of metformin on different types of cancer. Metformin acts by activating AMP-activated protein kinase (AMPK), a key player in the regulation of energy homeostasis. Moreover, by activating AMPK, metformin inhibits the mammalian target of rapamycin complex 1 (mtOrc1) resulting in decreased cancer cell proliferation. concomitantly, metformin induces activation of LKb1 (serine/threonine kinase 11), a tumor suppressor gene, which is required for the phosphorylation and activation of AMPK. these new encouraging experimental data supporting the anti-cancer effects of metformin urgently require further clinical studies in order to establish its use as a synergistic therapy targeting the AMPK/mtOr signaling pathway.
Metformin and cancer: Quo vadis et cui bono?
Oncotarget, 2015
How many lives have already been saved by the anti-cancer drug metformin? Inadvertently perhaps, among the millions of type 2 diabetics with occult or known cancers and who have been prescribed metformin since the 1950s, thousands may have benefited from the anticancer properties of this first-line pharmacotherapy. Quo vadis? Now, researchers aim to move metformin from a non-targeted stage of cancer therapy that has been mostly developed retrospectively and empirically into a targeted therapy by following a biological rationale and a predefined mechanism of action. But, who might benefit from metformin? Cui bono? Because metformin is on the leading edge of a new generation of cancer metabolism-targeted therapies, perhaps it is the right time to provide solutions to the challenges that metformin and other onco-biguanides will face in the coming years before becoming incorporated into the therapeutic armamentarium against cancer.
New Perspective for an Old Antidiabetic Drug: Metformin as Anticancer Agent
Cancer Treatment and Research, 2013
Metformin, an inexpensive, well-tolerated oral agent that is commonly used in the first-line treatment for type 2 diabetes, has become the focus of intense research as a potential anticancer agent. This research reflects a convergence of epidemiologic, clinical, and preclinical evidence, suggesting that metformin may lower cancer risk in diabetics and improve outcomes of many common cancers. Notably, metformin mediates an approximately 30 % reduction in the lifetime risk of cancer in diabetic patients. There is growing recognition that metformin may act (1) directly on cancer cells, primarily by impacting mitochondrial respiration leading to the activation of the AMP-activated protein kinase (AMPK), which controls energy homeostasis in cells, but also through other mechanisms or (2) indirectly on the host metabolism, largely through AMPK-mediated reduction in hepatic gluconeogenesis, leading to reduced circulating insulin levels and decreased insulin/IGF-1 receptor-mediated activation of the PI 3 K pathway. Support for this comes from the observation that metformin inhibits cancer cell growth in vitro and delays the onset of tobacco carcinogen-induced lung cancer in mice and that metformin and its