Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

Chen, Ying; Chou, Wei-Chung; Ding, Youming; Wu, Ya‐Chieh

doi:10.1159/000362966

Cited by 25 publications

(25 citation statements)

References 31 publications

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“…and ROS, inactivates extracellularsignal-regulated kinase (ERK) and activates p38 mitogenactivated protein kinase (MAPK) (Liu and Chang 2010;Lu et al 2014). Caffeine was also reported to inhibit the migration of rat and human glioma cells and down-regulate the expression of phosphorylated (p)-FAK and p-paxillin, two proteins involved in the formation of focal adhesions (Chen et al 2014b).…”

Section: Invasion and Metastasis Inhibitorsmentioning

confidence: 99%

Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer

2015

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Coffee is the second most popular beverage in the world after water with a consumption of approximately two billion cups per day. Due to its low cost and ease of preparation, it is consumed in almost all countries and by all social classes of the population through different modes of preparation. Despites its simple appearance, a cup of coffee is in fact a complex mixture that contains hundreds of molecules, the composition and concentration of which vary widely and depend on factors including the origin of the coffee tree or its metabolism. Although an excessive consumption of coffee can be harmful, many molecules that are present in this black decoction exert anticancer properties. This review aims to describe the different primary coffee-containing substances that exert chemopreventive and bioactive activities against the different hallmarks and enabling characteristics of cancer, thus explaining the anticancer health benefit of black coffee.

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Section: Invasion and Metastasis Inhibitorsmentioning

confidence: 99%

Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer

2015

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“…Caffeine and theophylline have been proposed to suppress the beneficial clinical effects of MTX through adenosine receptor antagonism . However, it is conceivable that caffeine and theophylline may interfere with the therapeutic effects of MTX through multiple mechanisms since they also target inositol 1,4,5‐trisphosphate (IP3) receptors, GABA receptors, ryanodine receptors, cyclic nucleotide phosphodiesterases (PDEs) and the ROCK‐FAK pathway that participate in the regulation of basic T‐cell functions .…”

Section: Introductionmentioning

confidence: 99%

Methotrexate and its therapeutic antagonists caffeine and theophylline, target a motogenic T‐cell mechanism driven by thrombospondin‐1 (TSP‐1)

2016

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Methotrexate (MTX) is a widely used treatment for inflammatory diseases such as rheumatoid arthritis and psoriasis, based on the concept that it is immunosuppressive.Its mechanism of action, however, remains unclear, although it is thought to depend on adenosine. Caffeine and theophylline, which have several targets including adenosine receptors, have been shown to suppress the beneficial clinical effects of MTX. Here we show that MTX and caffeine and theophylline differentially affect a motogenic T-cell mechanism driven by endogenous thrombospondin-1 (TSP-1) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1). MTX stimulated TSP-1 expression and the motogenic TSP-1/TSP-1 receptor mechanism in primary human T cells, hence mimicking IL-2 and CXCL12, which similar to MTX, dampen inflammatory disease. SiRNAmediated gene silencing of TSP-1 and LRP1 inhibited this stimulatory effect. Caffeine and theophylline inhibited the TSP-1/TSP-1 receptor mechanism by inhibiting LRP1 expression. These results indicate that the effect of MTX on T cells is immunoregulatory rather than immunosuppressive, and suggest a pathway dependent on TSP-1/TSP-1 receptor interactions for the regulation of immune responses.Keywords: Cytokines r Lipoprotein receptor related protein1 r Lymphocytes r Methotrexate r Thrombospondin-1 Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe pharmacological treatment of inflammatory diseases of autoimmune and allergic origin plays a pivotal role for the possibility to dampen symptoms and control the disease process in affected individuals. Widespread chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, ulcerous colitis, vasculitis, psoriasis, and multiple sclerosis, often require Correspondence: Prof. Karl-Gösta Sundqvist e-mail: Karl.Sundqvist@karolinska.se extensive long-term treatment. These diseases are generally considered to reflect an overactive immune system owing to poor suppression by regulatory T (Treg) cells [1][2][3][4][5]. Accordingly, the treatments applied are based on an immunosuppressive concept, which includes cytostatics, glucocorticoids, and an increasing number of so-called biological treatments in the form of monoclonal antibodies to lymphocytes and cytokines.MTX is a cornerstone immunosuppressive therapy for juvenile idiopathic arthritis, rheumatoid arthritis, and psoriasis and useful in inflammatory bowel disease, multiple sclerosis, vasculitis, and transplantation [6]. Although MTX is one of the most effective and Eur. J. Immunol. 2016. 46: 1279-1290 commonly used medicines to treat various forms of autoimmune diseases, the mechanism of action of MTX remains unclear. MTX is a folic acid antagonist but its immunosuppressive effects are thought to be mediated through the anti-inflammatory signaling molecule adenosine [7][8][9][10][11][12]. Adenosine is produced by Treg cells, promotes their immunoregulatory activity, and is an integral part of the immune reg...

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“…Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults [1,2]. Despite of therapeutic advances, the median survival of GBM patients is only about 15 months after diagnosis [3,4].…”

Section: Introductionmentioning

confidence: 99%

Impact of Autophagy Inhibition at Different Stages on Cytotoxic Effect of Autophagy Inducer in Glioblastoma Cells

Liu²,

Liu³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a poor prognosis. Combination treatment of autophagy inducer and autophagy inhibitor may be a feasible solution to improve the therapeutic effects. However, the correlation between them is unclear. The purpose of this study was to investigate the effect of autophagy inhibition at different stages on cytotoxicity of autophagy inducers in glioblastoma cells. Methods: Autophagy inhibition at early stage was achieved by 3-methyladenine (3-MA) or Beclin 1 shRNA. Autophagy inhibition at late stage was achieved by chloroquine (CQ) or Rab7 shRNA. Cell viability was assessed by MTT assay. Autophagy was measured using transmission electron microscopy and western blot. Apoptosis was measured using western blot and flow-cytometry. Results: Inhibition of early steps of autophagy by 3-MA or Beclin 1 knockdown decreased the toxic effect of arsenic trioxide (ATO) in GBM cell lines. In contrast, blockade of autophagy flux at late stage by CQ or Rab7 knockdown enhanced the cytotoxicity of ATO, and caused accumulation of degradative autophagic vacuoles and robust apoptosis. Moreover, depletion of Beclin 1 abolished the synergistic effect of ATO and CQ by reducing autophagy and apoptosis. Combination of CQ with other autophagy inducers also induced synergistic apoptotic cell death. Conclusion: These results suggest that inhibition of late process of autophagy, not initial step, increases the cytotoxic effect of autophagy inducers via autophagy and apoptosis, which may contribute to GBM chemotherapy.

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Caffeine Inhibits Migration in Glioma Cells through the ROCK-FAK Pathway

Cited by 25 publications

References 31 publications

Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer

Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer

Methotrexate and its therapeutic antagonists caffeine and theophylline, target a motogenic T‐cell mechanism driven by thrombospondin‐1 (TSP‐1)

Impact of Autophagy Inhibition at Different Stages on Cytotoxic Effect of Autophagy Inducer in Glioblastoma Cells

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