Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells

Sun, Fenyong; Han, Dan; Cao, Boqiang; Wang, Bo; Dong, Nan; Jiang, Dehua

doi:10.1007/s13277-015-4180-x

Cited by 21 publications

(16 citation statements)

References 27 publications

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“…Bim is essential for the death of neurocyte, epithelium cardiomyocyte and oncocytes [38–40]. Sun et al report that Foxo1 enhances the transcription of its pro-apoptotic target Bim , and Foxo1-Bim mediates caffeine-induced regression of glioma growth by activating cell apoptosis [41]. In our study, we also confirmed Foxo1 is a positive transcription factor of Bim in adipocytes.…”

Section: Discussionsupporting

confidence: 87%

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Cao

et al. 2017

Oncotarget

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Alpha-melanocyte stimulating hormone (αMSH) is an important adenohypophysis polypeptide hormone that regulates body metabolic status. To date, it is well known that the disorder of hypothalamic αMSH secretion is related to many metabolic diseases, such as obesity and type II diabetes. However, the underlying mechanisms are poorly understood. In our study, we focused on the reactive oxygen species (ROS)-induced adipocyte apoptosis and tried to unveil the role of αMSH in this process and the signal pathway which αMSH acts through. Kunming white mice were used and induced to oxidative stress status by hydrogen peroxide (H2O2) injection and a significant reduction of αMSH were found in mice serum, while elevated ROS level and mRNA level of pro-apoptotic genes were observed in mice adipose tissue. What is more, when detect the function of αMSH in ROS-induced apoptosis, similar inhibitory trend was found with the oxidative stress inhibitor N-acetyl-L-cysteine (NAC) in ROS-induced adipocyte apoptosis and this trend is αMSH receptor melanocortin 5 receptor (MC5R) depended, while an opposite trend was found between αMSH and Foxo1, which is a known positive regulator of adipocyte apoptosis. Further, we found that the repress effect of αMSH in adipocytes apoptosis is acting through Foxo1/mTORC2 pathway. These findings indicate that, αMSH has a strong inhibitory effect on ROS-induced adipocyte apoptosis and underlying mechanism is interacting with key factors in mTOR signal pathway. Our study demonstrated a great role of αMSH in adipocyte apoptosis and brings a new therapeutic mean to the treatment of obesity and diabetes.

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Section: Discussionsupporting

confidence: 87%

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Cao

et al. 2017

Oncotarget

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“…Serum and glucocorticoid-regulated kinase isoform 1, extracellular signal-regulated kinase, inhibitor of nuclear factor-κB kinase, and AMP-activated protein kinase have also been described as negative regulators of FOXO1 ( 30 , 31 ). Together, this suggests that FOXO1 is a convergence target for several signaling pathways and has an opposing role in tumorigenesis ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Trifluoperazine prevents FOXO1 nuclear excretion and reverses doxorubicin-resistance in the SHG44/DOX drug-resistant glioma cell line

2018

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As a tumor suppressor, Forkhead box O1 (FOXO1) is located in the nucleus where it regulates gene expression and inhibits tumor progression. However, the antitumor effects of FOXO1 are attenuated in several tumors due to its translocation from the nucleus to the cytoplasm. Trifluoperazine (TFP) is able to reverse tumor drug resistance by inhibiting multidrug resistance (MDR), however, the detailed molecular mechanisms by which this occurs remain to be fully elucidated. In the present study, the doxorubicin (DOX)-resistant SHG44/DOX glioma cell line was established. The results showed that TFP promoted DOX-induced cytotoxicity, cell cycle arrest and early apoptosis using a Cell Counting Kit-8 and flow cytometry. In vivo experiments also demonstrated that DOX combined with TFP reduced tumor volumes and proliferation indices, and led to higher protein levels of FOXO1. In addition, TFP inhibited the nuclear exclusion of FOXO1, contributing toward the downregulation of MDR genes and an increase in intracellular DOX concentrations by reverse transcription-quantitative polymerase chain reaction, western blot analysis, immunofluorescence and spectrophotometer analysis. Therefore, TFP may inhibit DOX resistance by stimulating FOXO1 nuclear translocation and suppressing MDF genes in SHG44/DOX cells, contributing to promising clinical prospects for tumor chemotherapy.

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“…Caffeine, a 1,3,7-trimethylxanthine derivative, is a potential anticancer drug that inhibits cell proliferation and induces apoptosis on various cancer cells in vitro and in vivo (135)(136)(137). The alternative splicing of cancer-related genes is involved in caffeine-induced antitumor function, including p53, PKM2, and hypoxia-inducible factor-1α/2α (HIF-1α/2α) (80,(138)(139)(140).…”

Section: Implications For Therapymentioning

confidence: 99%

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer

et al. 2020

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Ser/Arg-rich (SR) proteins are RNA-binding proteins known as constitutive and alternative splicing (AS) regulators that regulate multiple aspects of the gene expression program. Ser/Arg-rich splicing factor 3 (SRSF3) is the smallest member of the SR protein family, and its level is controlled by multiple factors and involves complex mechanisms in eukaryote cells, whereas the aberrant expression of SRSF3 is associated with many human diseases, including cancer. Here, we review state-of-the-art research on SRSF3 in terms of its function, expression, and misregulation in human cancers. We emphasize the negative consequences of the overexpression of the SRSF3 oncogene in cancers, the pathways underlying SRSF3-mediated transformation, and implications of potential anticancer drugs by downregulation of SRSF3 expression for cancer therapy. Cumulative research on SRSF3 provides critical insight into its essential part in maintaining cellular processes, offering potential new targets for anti-cancer therapy.

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Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells

Cited by 21 publications

References 27 publications

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

αMSH prevents ROS-induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue

Trifluoperazine prevents FOXO1 nuclear excretion and reverses doxorubicin-resistance in the SHG44/DOX drug-resistant glioma cell line

Emerging Roles of SRSF3 as a Therapeutic Target for Cancer

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