36
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Metformin alters signaling induced crosstalk and homeostasis in the carcinogenesis paradigm “Epistemology of the origin of cancer”

      review-article
      1 , 2 , 3 , * , , 1 , 2 , 4
      4open
      EDP Sciences
      Akt, ALL, ALK-1, AMP, AMPK, Apoptosis, Autophagy, Bax, Bcl-2, BrDU, Breast cadherin, Cancer, Carcinogenesis, Cell transition, Chronic inflammation, Collagen, Collagenase, Colon, CCC, Cox-1, Cox-2, CRP, CXCL8, Decorin, Diabetes, DNA, EGFR, Elastin, Elastase, Endometrium, Epidemiology, Epigenetics, Erk, Fibronectin, Fibrosis, FOXO3a, Genetics, Genomics, GRIM-19, GTPase, HCC, HER2/neu, HIF-1α, HPV, Interleukin, Keratin, Keratinase, KRAS; liver, LOX, MAPK, MCP1, Metastasis, Metformin, Microbiome, microRNA, MMP, mTOR, mTORC1, Mutation, NF-κB, NLRP3, NRF-2, NSCLC, Ovary, PAI-1, PARP, Pathogenesis, PCK, PEPCK, PGE2, PPA2, Precancerous niche, Proteomics, Pyroptosis, RNA, Signaling, Snail, Somatic mutation theory, STAT3, T2D, TGF, TIMP1, Vimentin, Virus

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The anti-hyperglycemic drug, Metformin, is effective in treating early stages of diabetes and has been associated with a 37% decrease in cancer incidence. While the precise mechanisms for the anti-cancer effects of Metformin remain to be elucidated, this review shows the multiplicity of its effects on interdicting signaling and crosstalk, anti-inflammatory effects and in restoring homeostasis, which, taken together, go beyond its well-known anti-hyperglycemic effect that serves as the basis for its use in type 2 diabetes. Metformin is much more than a one-trick pony. The recent discovery of several signaling pathways influenced by Metformin appears to have potential value in cancer therapy. Based on what we know at present, Metformin promotes beneficial effects attributed to its anti-inflammatory and anti-fibrotic effects largely demonstrated in vitro. Metformin activates or upregulates while it simultaneously inhibits or downregulates multiple signaling pathways of cell-cycle arrest and apoptosis accompanied by oxidative stress, which are in accordance with the 6-step sequence of carcinogenesis. Furthermore, in vivo studies in laboratory animals and in cancer patients are beginning to address the magnitude of the anti-cancer effects and delineate its anti-cancer effects. In this context, results from prior pancreatic and non-pancreatic cancer trials, which contained a significant proportion of the patient population treated with Metformin, will have to be reexamined in light of the observed anti-cancerous effects to gain additional insights. The detailed exploration of Metformin in the context of the “ Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer ” can provide helpful insights into the anti-proliferative mechanisms and could play a relevant role in anti-cancer therapy in the future.

          Related collections

          Most cited references167

          • Record: found
          • Abstract: found
          • Article: not found

          Prevalence of childhood and adult obesity in the United States, 2011-2012.

          More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010. To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults. Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey. In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children (P = .03) and women (P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006). Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome.

            We have investigated the interrelationship between diet, gut microbial ecology, and energy balance using a mouse model of obesity produced by consumption of a prototypic Western diet. Diet-induced obesity (DIO) produced a bloom in a single uncultured clade within the Mollicutes class of the Firmicutes, which was diminished by subsequent dietary manipulations that limit weight gain. Microbiota transplantation from mice with DIO to lean germ-free recipients promoted greater fat deposition than transplants from lean donors. Metagenomic and biochemical analysis of the gut microbiome together with sequencing and metabolic reconstructions of a related human gut-associated Mollicute (Eubacterium dolichum) revealed features that may provide a competitive advantage to members of the bloom in the Western diet nutrient milieu, including import and processing of simple sugars. Our study illustrates how combining comparative metagenomics with gnotobiotic mouse models and specific dietary manipulations can disclose the niches of previously uncharacterized members of the gut microbiota.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

              A randomized clinical trial reveals that the antidiabetic effects of metformin are at least partially due to beneficial changes in the microbiota.
                Bookmark

                Author and article information

                Journal
                fopen
                https://www.4open-sciences.org
                4open
                4open
                EDP Sciences
                2557-0250
                25 April 2019
                25 April 2019
                2019
                : 2
                : ( publisher-idID: fopen/2019/01 )
                : 12
                Affiliations
                [1 ] Theodor-Billroth-Akademie® , , Germany, USA,
                [2 ] INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy® , , Germany, USA,
                [3 ] Department of Surgery, Carl-Thiem-Klinikum, , Cottbus, Germany,
                [4 ] Risk-Based Decisions Inc., , Sacramento, CA, USA,
                Author notes
                [* ]Corresponding author: b-bruecher@ 123456gmx.de
                Author information
                https://orcid.org/0000-0002-3930-6416
                Article
                fopen180009
                10.1051/fopen/2019006
                278741e5-7be9-4b0c-87ab-69599fa98a3a
                © B.L.D.M. Brücher & I.S. Jamall, Published by EDP Sciences, 2019

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 March 2018
                : 04 March 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 166, Pages: 17
                Categories
                Life Sciences - Medicine
                Review Article
                Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”
                Custom metadata
                yes
                4open 2019, 2, 12
                2019
                2019
                2019

                Medicine,Chemistry,Physics,Mathematics,Materials science,Life sciences
                Cancer,PEPCK,CXCL8,NF-κB,AMP,MAPK,Snail,mTORC1,EGFR,Metformin,MMP,microRNA,Somatic mutation theory,HIF-1α,Endometrium,KRAS; liver,PGE2,RNA,Akt,Genomics,TGF,Proteomics,Fibrosis,NLRP3,BrDU,Erk,Mutation,AMPK,Pyroptosis,Epidemiology,FOXO3a,ALL,TIMP1,Keratin,mTOR,HCC,DNA,Metastasis,MCP1,Keratinase,PPA2,Apoptosis,CRP,Carcinogenesis,Genetics,HER2/neu,Decorin,Elastase,Epigenetics,Elastin,Pathogenesis,Fibronectin,Signaling,GRIM-19,Colon,NRF-2,HPV,LOX,Ovary,Microbiome,Autophagy,CCC,Bax,Cell transition,Diabetes,T2D,Bcl-2,Cox-2,Breast cadherin,Collagenase,Collagen,Vimentin,Chronic inflammation,ALK-1,Virus,Cox-1,GTPase,STAT3,NSCLC,Interleukin,Precancerous niche,PAI-1,PARP,PCK

                Comments

                Comment on this article