Metformin reduces the Walker-256 tumor development in obese-MSG rats via AMPK and FOXO3a

Queiroz, Eveline Aparecida Isquierdo Fonseca de; Akamine, Eliana Hiromi; Carvalho, Maria Helena Catelli de; Sampaio, Sandra Coccuzzo; Fortes, Zuleica Bruno

doi:10.1016/j.lfs.2014.11.028

Cited by 16 publications

(14 citation statements)

References 67 publications

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“…The development of the tumor was higher in obese-MSG tumor rats compared to control tumor rats. Activation of the insulin-IR-ERK1/2 pathway and an anti-apoptotic effect might be the mechanisms involved in the higher development of tumors in obesity (de Queiroz, Akamine, de Carvalho, Sampaio, & Fortes, 2015;Fonseca et al, 2011).…”

Section: Promotion Of Tumor Development In Msg-induced Obesitymentioning

confidence: 99%

A Review of the Alleged Health Hazards of Monosodium Glutamate

Zanfirescu

Ungurianu

Tsatsakis

et al. 2019

Comp Rev Food Sci Food Safe

168

142

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Monosodium glutamate (MSG) is an umami substance widely used as flavor enhancer. Although it is generally recognized as being safe by food safety regulatory agencies, several studies have questioned its long‐term safety. The purpose of this review was to survey the available literature on preclinical studies and clinical trials regarding the alleged adverse effects of MSG. Here, we aim to provide a comprehensive overview of the reported possible risks that may potentially arise following chronic exposure. Preclinical studies have associated MSG administration with cardiotoxicity, hepatotoxicity, neurotoxicity, low‐grade inflammation, metabolic disarray, and premalignant alterations, along with behavioral changes. However, in reviewing the available literature, we detected several methodological flaws, which led us to conclude that these studies have limited relevance for extrapolation to dietary human intake of MSG risk exposure. Clinical trials have focused mainly on MSG effects on food intake and energy expenditure. Besides its well‐known impact on food palatability, MSG enhances salivary secretion and interferes with carbohydrate metabolism, while the impact on satiety and post‐meal recovery of hunger varied in relation to meal composition. Reports on MSG hypersensitivity or links of its use to increased pain sensitivity and atopic dermatitis were found to have little supporting evidence. Many of the reported negative health effects of MSG have little relevance for chronic human exposure and are poorly informative as they are based on excessive dosing that does not meet with levels normally consumed in food products. We conclude that further clinical and epidemiological studies are needed, with an appropriate design, accounting for both added and naturally occurring dietary MSG.

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Section: Promotion Of Tumor Development In Msg-induced Obesitymentioning

confidence: 99%

A Review of the Alleged Health Hazards of Monosodium Glutamate

Zanfirescu

Ungurianu

Tsatsakis

et al. 2019

Comp Rev Food Sci Food Safe

168

142

View full text Add to dashboard Cite

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“…To date, many drugs associated with obesity such as lipid-lowering (statins) or antidiabetic drugs (metformin) have been used in cancer treatment with good effects (Brown, 2007;De Queiroz et al, 2015;Hager et al, 2006;Hanai et al, 2012;Wang et al, 2014). Appropriately, it has been demonstrated that both statins and metformin are able to increase the activity of FOXO3 (De Queiroz et al, 2015;Wolfe et al, 2015), whereas metformin is also able to inhibit the expression of FOXM1 . Collectively, these observations advocate further that targeting lipid metabolism in conjunction with the FOXO3-FOXM1 axis maybe a viable strategy for tackling cancer development, progression and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis

Saavedra‐García

Nichols

Mahmud

et al. 2018

Molecular and Cellular Endocrinology

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Keywords:Fatty acids Cancer Lipid metabolism FOXO3 FOXM1 AKT/PI3K pathway a b s t r a c t Obesity and cachexia represent divergent states of nutritional and metabolic imbalance but both are intimately linked to cancer. There is an extensive overlap in their signalling pathways and molecular components involved such as fatty acids (FAs), which likely play a crucial role in cancer. Forkhead box (FOX) proteins are responsible of a wide range of transcriptional programmes during normal development, and the FOXO3-FOXM1 axis is associated with cancer initiation, progression and drug resistance.Free fatty acids (FFAs), FA synthesis and b-oxidation are associated with cancer development and progression. Meanwhile, insulin and some adipokines, that are up-regulated by FAs, are also involved in cancer development and poor prognosis. In this review, we discuss the role of FA metabolism in cancer and how FA metabolism integrates with the FOXO3-FOXM1 axis. These new insights may provide leads to better cancer diagnostics as well as strategies for tackling cancer development, progression and drug resistance.

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“…Yang et al (2006) showed that the fermentation broth containing a mixture of polysaccharides derived from Antrodia camphorate, as well as other chemicals, induced cell-death in a dose-and time-dependent manner in MCF-7 cells, and that this effect was associated with an increase in apoptosis and ROS generation. In another study, Weng et al (2011) The LKB1/AMPK pathway (serine/threonine kinase LKB1 (Liver Kinase B1), a tumor suppressor and key upstream activator of AMPK through direct phosphorylation, Shackelford and Shaw 2009) serves as a metabolic checkpoint in the cell, and has been described as an important pathway in the inhibition of cellular growth and promotion of apoptosis in cancer cells by inhibiting mTOR and p70S6K activities, as well as by activating p53 protein (Berstein et al, 2010;Feng et al, 2007;Queiroz et al, 2014;Queiroz et al, 2015;Zakikhani et al, 2008). In addition, studies have shown that AMPK can activate the Forkhead transcription factor, FOXO proteins, in conditions such as nutrient deprivation thereby increasing cell survival (Chiacchiera et al, 2009;Greer et al, 2009).…”

Section: Discussionmentioning

confidence: 99%