FOXO1 Inhibits Tumor Cell Migration via Regulating Cell Surface Morphology in Non-Small Cell Lung Cancer Cells

Gao, Zhuo; Liu, Ruiqi; Ye, Na; Liu, Chao; Li, Xiuli; Guo, Xiaodong; Zhang, Zhuoran; Li, Xiaoxi; Yao, Yuanfei; Jiang, Xiaofeng

doi:10.1159/000491670

Cited by 33 publications

(25 citation statements)

References 32 publications

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“…The cell skeleton which regulates cell polarity and morphology plays an essential role in cell migration and adhesion as well. In our study, morphological analysis after staining with crystal violet shows that cells are elongated, and cell shapes are correlated with migration status [23,24], in a concentration-dependent manner from 5 to 25 μM ( Fig. 2a).…”

Section: Silibinin Promotes Migration Of C2c12 Myoblasts In a Concentsupporting

confidence: 51%

Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down-regulation of estrogen receptor α expression

et al. 2020

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Skeletal muscle regeneration is a complex process, involving the proliferation, migration, and differentiation of myoblasts. Recent studies suggest that some natural flavanones stimulate myogenesis. However, the effect of plant estrogen, silibinin, on the regulation of myoblast behaviors is unclarified. In this study, we investigated the effects of silibinin on immortalized murine myoblast C2C12 in the aspects of proliferation, migration, differentiation along with underlying mechanisms. The results show that silibinin at concentrations below 50 μM enhanced the migration and differentiation of C2C12 cells, but had no effect on cell proliferation. Silibinin significantly promoted the production of ROS, which appeared to play important roles in the migration and differentiation of the myoblasts. Interestingly, among ROS, the superoxide anion and hydroxyl radical were associated with the migration, whereas hydrogen peroxide contributed to the myogenic differentiation. We used ER agonist and antagonist to explore whether estrogen receptors (ERs), which are affected by silibinin treatment in the silibinin-enhanced C2C12 migration and differentiation. Migration was independent of ERs, whereas the differentiation was associated with decreased ERα activity. In summary, silibinin treatment increases ROS levels, leading to the promotion of migration and myogenic differentiation. Negative regulation ERα of differentiation but not of migration may suggest that ERα represses hydrogen peroxide generation. The effect of silibinin on myoblast migration and differentiation suggests that silibinin may have therapeutic benefits for muscle regeneration.

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Section: Silibinin Promotes Migration Of C2c12 Myoblasts In a Concentsupporting

confidence: 51%

Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down-regulation of estrogen receptor α expression

et al. 2020

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“…Epigenetic regulation, especially phosphorylation by AKT serine/threonine kinase (Akt), could promote its degradation and dysfunction [6]. Importantly, FoxO factors have been identified as tumour suppressors involved in the biological behaviours of cancer cells, such as extracellular matrix degradation, angiogenesis and migration [7][8][9]. FoxO factors are involved in regulating the genes associated with cellular cycle progression and inducing apoptosis [10].…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Sun

Wang

et al. 2019

Cells

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Background: The present study was designed to explore the underlying role of hypoxia-inducible factor 1α (HIF-1α) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. Methods: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1α expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information's Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1α and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1α. We inhibited HIF-1α via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As 2 O 3 treatment. Results: Ad interim knockdown of HIF-1α also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1α silencing via siRNA. Conclusions: Our data reveal that HIF-1α inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1α inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As 2 O 3 ) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

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“…FoxO1 negatively regulates the growth of lung cancer tumor cells in mice [44]. Increased FoxO3 expression enhances radiation resistance in NSCLC cells [45]. This study found that the active ingredients of Shenlian Capsule act on 17 proteins related to the FoxO signaling pathway.…”

Section: Discussionmentioning

confidence: 72%

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

Gong

Wei

et al. 2020

Preprint

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Background: Shenlian Capsule is a Chinese medicine compound approved by the China Food and Drug Administration (CFDA) for the treatment of advanced non-small cell lung cancer(NSCLC). However, due to its complex constituents, cause its effective active compounds and main action mechanisms for treating diseases are still not fully clear. The purpose of this work is to explore the active ingredients and mechanisms of Shenlian Capsule treatment NSCLC through a system pharmacological approach. Methods: First, a database of Shenlian Capsule chemical composition was constructed by retrieving Chinese herbal medicine data. Absorption, distribution, metabolism and excretion (ADME) methods were used to screen potential active compounds. Predict active compound targets with a large-scale molecular network target prediction technology. Clustering of active compounds obtained through cluster analysis by MECODE plug-in, each cluster obtains the main pathways through enrichment analysis method. To get all targets related to survival in NSCLC, the survival related targets were intersected with the compounds target (C-T) network to get the survival related targets for Shenlian Capsule. Finally, a batch molecular docking technique was used to verify the effect of active compounds of Shenlian Capsule on survival-related targets.Results: The Shenlian Capsule C-T network was constructed with 117 potential compounds and 47 targets. Treatment of NSCLC with Shenlian Capsule through enrichment analysis may involve multiple pathways such as anti-inflammatory, immune regulation, regulation of cell cycle, apoptosis, antiviral, cell hypoxia, angiogenesis and so on. Shenlian Capsule has eight survival-related genes in non-small cell lung adenocarcinoma (LUAD) and two survival-related genes in non-small cell squamous cell lung carcinoma (LUSC). It is known through molecular docking that the active compound has lower energy after conformation with survival-related genes, and has lower binding energy and stable binding.Conclusion: In this study, the potential compounds of active compounds in Shenlian Capsule were first predicted using network pharmacology technology. Through the enrichment analysis, the main pathways of the role of Shenlian Capsule were outcropped. Secondly, by combining bioinformatics and network pharmacology, Shenlian Capsule can be regulated to target survival-related targets. Finally, the molecular docking technique shows the relationship between active compounds and survival-related targets after docking. This work provided a scientific basis for the clinical role of Shenlian Capsule in the treatment of NSCLC, provided a research basis for further clarifying the active ingredients and mechanism of Shenlian Capsule in the treatment of NSCLC.

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FOXO1 Inhibits Tumor Cell Migration via Regulating Cell Surface Morphology in Non-Small Cell Lung Cancer Cells

Cited by 33 publications

References 32 publications

Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down-regulation of estrogen receptor α expression

Natural flavonoid silibinin promotes the migration and myogenic differentiation of murine C2C12 myoblasts via modulation of ROS generation and down-regulation of estrogen receptor α expression

Metabolism of Reactive Oxygen Species in Osteosarcoma and Potential Treatment Applications

Uncovering the Mechanism of Shenlian Capsules in the Treatment of Non-small Cell Lung Cancer by System Pharmacology

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