scholarly journals Metformin – its potential anti-cancer and anti-aging effects

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Monika Podhorecka ◽  
Blanca Ibanez ◽  
Anna Dmoszyńska
Keyword(s):  
Metabolic Stress ◽  
Glucose Deprivation ◽  
Adenosine Monophosphate ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Anti Cancer ◽  
Aging Properties ◽  
Treatment Of Diabetes ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

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. The aim of this review is to describe the potential anti-cancer and anti-aging properties of metformin and discuss the possible underlying mechanisms.

scholarly journals Metformin - its anti-cancer effects in hematologic malignancies

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Monika Podhorecka
Keyword(s):  
Adenosine Monophosphate ◽  
Hematologic Malignancies ◽  
Aging Effects ◽  
Hematological Disorders ◽  
Beneficial Effects ◽  
Wide Range ◽  
Anti Cancer ◽  
Great Progress ◽  
Amp Activated Protein Kinase ◽  
Effective Drugs

The main anti-diabetic effect of metformin mediated through stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) is the inhibition of hepatic gluconeogenesis and triggering glucose uptake in skeletal muscles. Additionally, some new pathways, besides the AMPK activation, were discovered, that can explain wide-range properties of metformin. All these properties are now attracting the attention of researchers in the fields other than diabetes and the drug has been reported to have anti-cancer, immunoregulatory and anti-aging effects. Among others, the beneficial effects of metformin in hematological disorders like leukemias, lymphomas, and multiple myeloma were reported. Despite a great progress in therapy, these diseases are still incurable in most cases. Thus, there is an urgent need to discover novel, less toxic and more effective drugs especially for older or chemotherapy-resistant patients. In this review article, the current findings on the anti-cancer effect of metformin together with underlying possible mechanisms in blood cancers are discussed. However. to evaluate precisely these promising effects of metformin, more studies are required, because many of the published results are preclinical.

Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK

2001 ◽  
Vol 355 (2) ◽  
pp. 297-305 ◽  
Author(s):  
Diana L. LEFEBVRE ◽  
Yahong BAI ◽  
Nazanin SHAHMOLKY ◽  
Monika SHARMA ◽  
Raymond POON ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cellular Response ◽  
Catalytic Domain ◽  
Metabolic Stress ◽  
Glucose Deprivation ◽  
Protein Band ◽  
Northern Blotting ◽  
Significant Similarity ◽  
Amp Activated Protein Kinase

Subtraction hybridization after the exposure of keratinocytes to ultraviolet radiation identified a differentially expressed cDNA that encodes a protein of 630 amino acid residues possessing significant similarity to the catalytic domain of the sucrose-non-fermenting protein kinase (SNF1)/AMP-activated protein kinase (AMPK) family of serine/threonine protein kinases. Northern blotting and reverse-transcriptase-mediated PCR demonstrated that mRNA transcripts for the SNF1/AMPK-related kinase (SNARK) were widely expressed in rodent tissues. The SNARK gene was localized to human chromosome 1q32 by fluorescent in situ hybridization. SNARK was translated in vitro to yield a single protein band of approx. 76kDa; Western analysis of transfected baby hamster kidney (BHK) cells detected two SNARK-immunoreactive bands of approx. 76-80kDa. SNARK was capable of autophosphorylation in vitro; immunoprecipitated SNARK exhibited phosphotransferase activity with the synthetic peptide substrate HMRSAMSGLHLVKRR (SAMS) as a kinase substrate. SNARK activity was significantly increased by AMP and 5-amino-4-imidazolecarboxamide riboside (AICAriboside) in rat keratinocyte cells, implying that SNARK might be activated by an AMPK kinase-dependent pathway. Furthermore, glucose deprivation increased SNARK activity 3-fold in BHK fibroblasts. These findings identify SNARK as a glucose- and AICAriboside-regulated member of the AMPK-related gene family that represents a new candidate mediator of the cellular response to metabolic stress.

scholarly journals Anti-aging properties of metformin

2021 ◽  
Vol 11 (9) ◽  
pp. 37-42
Author(s):  
Anna Małgorzata Łopuszyńska ◽  
Mateusz Pawlicki ◽  
Magdalena Kozioł ◽  
Aleksandra Krasa ◽  
Ewa Piekarska ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Trials ◽  
Aging Effect ◽  
Oral Drug ◽  
Aging Effects ◽  
Ampk Signaling ◽  
Anti Cancer ◽  
Aging Properties ◽  
Effects Of Aging

 Introduction: Life expectancy of human population is being constantly prolonged, hence there is a lot of research into drug that will prevent the effects of aging. There are many reports that metformin, which is a drug used in type 2 diabetes, has anti-aging effects. It belongs to the group of biguanides and has been used since the 1950s. It is a relatively safe, cheap and effective drug, which makes it a promising subject for many studies. The purpose of this review is to present the latest developments in this field. Material and methods: PubMed scientific base was searched using following keywords: metformin, aging, anti-aging, in years 2017-2021. Results: Numerous studies show that metformin has an impact on aging through the nutrient pathway, AMPK signaling pathway, and its effects on reactive oxygen species. In addition, it has an anti-cancer effect, inhibiting, among others, rectal cancer cells and p53 mutant colon cancer. Research in rodents has shown that this drug has anti-aging effects on many organs, including the CNS, ovaries, prostate, heart muscle and skin. Conclusions: Metformin, which is the most commonly used oral drug in type 2 diabetes, has many other mechanisms of action. Its anti-aging effect works on many organs in our bodies, which gives hope to find an anti-aging substance. However, multicentre, randomized trials are needed to determine the exact anti-aging dose, its possible side effects, and effects on various organisms. 

scholarly journals The Role of AMPK/mTOR Signaling Pathway in Anticancer Activity of Metformin

2021 ◽  
pp. 501-508
Author(s):  
Nikola Chomanicova ◽  
Andrea Gazova ◽  
Adriana Adamickova ◽  
Simona Valaskova ◽  
Jan Kyselovic
Keyword(s):  
Anticancer Activity ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Mtor Pathway ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Treatment Of Diabetes

Metformin (MTF) is a widely used drug for the treatment of diabetes mellitus type 2 (DM2) and frequently used as an adjuvant therapy for polycystic ovarian syndrome, metabolic syndrome, and in some cases also tuberculosis. Its protective effect on the cardiovascular system has also been described. Recently, MTF was subjected to various analyzes and studies that showed its beneficial effects in cancer treatment such as reducing cancer cell proliferation, reducing tumor growth, inducing apoptosis, reducing cancer risk in diabetic patients, or reducing likelihood of relapse. One of the MTF’s mechanisms of action is the activation of adenosine-monophosphate-activated protein kinase (AMPK). Several studies have shown that AMPK/mammalian target of rapamycin (mTOR) pathway has anticancer effect in vivo and in vitro. The aim of this review is to present the anticancer activity of MTF highlighting the importance of the AMPK/mTOR pathway in the cancer process.

scholarly journals New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway

2021 ◽  
Vol 22 (17) ◽  
pp. 9453
Author(s):  
Sheng-Kai Hsu ◽  
Kai-Chun Cheng ◽  
Miracle Oluebube Mgbeahuruike ◽  
Yi-Hsiung Lin ◽  
Chang-Yi Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Diabetic Retinopathy ◽  
Metabolic Stress ◽  
Glucose Deprivation ◽  
Ampk Pathway ◽  
Anticancer Effects ◽  
Pathway Activation ◽  
Nonapoptotic Cell Death ◽  
Amp Activated Protein Kinase

Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.

scholarly journals Herba houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 164
Author(s):  
Ke Cao ◽  
Weiqiang Lv ◽  
Xuyun Liu ◽  
Yingying Fan ◽  
Kexin Wang ◽  
...  
Keyword(s):  
Adenosine Monophosphate ◽  
Poloxamer 407 ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Complex Activities

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

scholarly journals The Beneficial Effects of Principal Polyphenols from Green Tea, Coffee, Wine, and Curry on Obesity

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 453
Author(s):  
Tomokazu Ohishi ◽  
Ryuuta Fukutomi ◽  
Yutaka Shoji ◽  
Shingo Goto ◽  
Mamoru Isemura
Keyword(s):  
Green Tea ◽  
Animal Studies ◽  
Epigallocatechin Gallate ◽  
Nuclear Factor Κb ◽  
Epidemiological Studies ◽  
Ros Generation ◽  
Beneficial Effects ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Amp Activated Protein Kinase

Several epidemiological studies and clinical trials have reported the beneficial effects of green tea, coffee, wine, and curry on human health, with its anti-obesity, anti-cancer, anti-diabetic, and neuroprotective properties. These effects, which have been supported using cell-based and animal studies, are mainly attributed to epigallocatechin gallate found in green tea, chlorogenic acid in coffee, resveratrol in wine, and curcumin in curry. Polyphenols are proposed to function via various mechanisms, the most important of which is related to reactive oxygen species (ROS). These polyphenols exert conflicting dual actions as anti- and pro-oxidants. Their anti-oxidative actions help scavenge ROS and downregulate nuclear factor-κB to produce favorable anti-inflammatory effects. Meanwhile, pro-oxidant actions appear to promote ROS generation leading to the activation of 5′-AMP-activated protein kinase, which modulates different enzymes and factors with health beneficial roles. Currently, it remains unclear how these polyphenols exert either pro- or anti-oxidant effects. Similarly, several human studies showed no beneficial effects of these foods, and, by extension polyphenols, on obesity. These inconsistencies may be attributed to different confounding study factors. Thus, this review provides a state-of-the-art update on these foods and their principal polyphenol components, with an assumption that it prevents obesity.

scholarly journals Tissue-Type Plasminogen Activator Mediates Neuronal Detection and Adaptation to Metabolic Stress

2013 ◽  
Vol 33 (11) ◽  
pp. 1761-1769 ◽  
Author(s):  
Fang Wu ◽  
Andrew D Nicholson ◽  
Woldeab B Haile ◽  
Enrique Torre ◽  
Jie An ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Metabolic Stress ◽  
Glucose Deprivation ◽  
Adenosine Monophosphate ◽  
Tissue Type ◽  
Neuronal Uptake ◽  
Main Role ◽  
Ampk Activation ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

Adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor that regulates cellular adaptation to metabolic stress. Tissue-type plasminogen activator (tPA) is a serine proteinase found in the intravascular space, where its main role is as thrombolytic enzyme, and in neurons, where its function is less well understood. Here, we report that glucose deprivation induces the mobilization and package of neuronal tPA into presynaptic vesicles. Mass spectrometry and immunohistochemical studies show that the release of this tPA in the synaptic space induces AMPK activation in the postsynaptic terminal, and an AMPK-mediated increase in neuronal uptake of glucose and neuronal adenosine 5′(tetrahydrogen triphosphate; ATP) synthesis. This effect is independent of tPA's proteolytic properties, and instead requires the presence of functional N-methyl-D-aspartate receptors (NMDARs). In agreement with these observations, positron emission tomography (PET) studies and biochemical analysis with synaptoneurosomes indicate that the intravenous administration of recombinant tPA (rtPA) after transient middle cerebral artery occlusion (tMCAO) induces AMPK activation in the synaptic space and NMDAR-mediated glucose uptake in the ischemic brain. These data indicate that the release of neuronal tPA or treatment with rtPA activate a cell signaling pathway in the synaptic space that promotes the detection and adaptation to metabolic stress.

scholarly journals Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition

2019 ◽  
Vol 242 (2) ◽  
pp. R51-R65 ◽  
Author(s):  
M J Vazquez ◽  
I Velasco ◽  
M Tena-Sempere
Keyword(s):  
Metabolic Control ◽  
Pubertal Timing ◽  
Mammalian Target Of Rapamycin ◽  
Metabolic Stress ◽  
Adverse Health Outcomes ◽  
Reproductive Axis ◽  
Prevalence Of Obesity ◽  
Underlying Mechanisms ◽  
Genetically Determined ◽  
Amp Activated Protein Kinase

Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing the reproductive axis. The timing of puberty is genetically determined; yet, puberty is also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests that alterations of the age of puberty are becoming more frequent; the underlying mechanisms remain largely unknown, but the escalating prevalence of obesity and other metabolic/feeding disorders is possibly a major contributing factor. This phenomenon may have clinical implications, since alterations in pubertal timing have been associated to adverse health outcomes, including higher risk of earlier all-cause mortality. This urges for a better understanding of the neurohormonal basis of normal puberty and its deviations. Compelling evidence has recently documented the master role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine pathways controlling puberty. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. Key cellular metabolic sensors, as the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK) and the fuel-sensing deacetylase, SIRT1, have been recently shown to participate also in the metabolic modulation of puberty. Recently, we have documented that AMPK and SIRT1 operate as major molecular effectors for the metabolic control of Kiss1 neurons and, thereby, puberty onset. Alterations of these molecular pathways may contribute to the perturbation of pubertal timing linked to conditions of metabolic stress in humans, such as subnutrition or obesity and might become druggable targets for better management of pubertal disorders.

scholarly journals Selenium bio-fortification: an alternative to improve phytochemicals and bioactivities of plant foods

2017 ◽  
Vol 7 (4) ◽  
pp. 263 ◽  
Author(s):  
Rattanamanee Chomchan ◽  
Sunisa Siripongvutikorn ◽  
Panupong Puttarak
Keyword(s):  
Early Stage ◽  
Biological Properties ◽  
Food Sources ◽  
Negative Effects ◽  
Plant Foods ◽  
Beneficial Effects ◽  
Living Things ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Higher Doses

Background: Plants are the major food sources which possess marvelous health benefits and wellness to human. To date, the effort to improve composites in plants using bio-fortification technique is expedient in order to obtain super plant foods. Selenium (Se) is an essential trace element works on antioxidant system in living things. Se has been bio-fortified into plants worldwide to increase Se content in plants as well as improve some plant bioactive compounds and biological properties. However, restricted documents were elucidated on the summary and underlying mechanisms which provide beneficial effects on plant phytochemicals and bioactivities improvement. This review attempts to study available literatures on Se bio-fortified plants and clarified possible routes that Se may effect to plants. Increasing the content of Se bio-fortified to plants resulted in both positive and negative effects. The appropriate exogenous concentration of Se bio-fortified to individual plants which can support growth or induce them to the early stage of stress are the vital strategic to provide desired effects on an improvement of phytochemicals, for example, chlorophyll, phenolic compounds, ascorbic acid. Moreover, the greater antioxidant, anti-cancer and prebiotic properties were also reported while higher doses of Se were toxic to plants. Consequently, Se bio-fortification can be claimed as a unique strategy to improve plant treasures.Keywords: Selenium, Bio-fortification, Phytochemicals, Bioactivities

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