EX527, a Sirt-1 inhibitor, induces apoptosis in glioma via activating the p53 signaling pathway

Sirtuin-1 (Sirt-1), an NAD-dependent deacetylase, promotes tumorigenesis in glioma; however, whether the Sirt-1 specific inhibitor, EX527 exerts antitumor effects and the underlying mechanism in glioma requires further investigation. In the present study, the proliferative and colony formation abilities of two glioma cell lines (U87MG and LN-299) were inhibited by EX527. Treatment with EX527 increased the number of apoptotic cells (Annexin V-fluorescein isothiocyanate+/propidium iodide+/−); pretreatment with the caspase inhibitor Z-VAD-FMK suppressed EX527-induced apoptosis, suggesting that EX527 induced caspase-dependent apoptosis. In addition, western blotting revealed that EX527 treatment increased the expression of cleaved-caspase-3, poly (ADP-ribose) polymerase-1, B-cell lymphoma 2 (Bcl-2)-associated-X-protein and Bcl-2-like 11 but decreased that of Bcl-2. p53 is deacetylated by Sirt-1, attenuating its function. Furthermore, EX527 upregulated the expression of p53, acetylated p53 and the p53 target gene p21. This result suggests that EX527 induced cell apoptosis by activating p53 in glioma. Of note, EX527 exhibited antitumor effects on patient-derived glioma cells under three-dimensional culture conditions. Collectively, the results of the present study indicated that EX527 may be used as an effective compound in the treatment of glioma.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research

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Contributors : Anuhar Chaturvedi ; Michael HeuserSeries Type : Expression profiling by arrayOrganism : Homo sapiensMutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis. Data for IDH1 inhibitors show that 30-40% of AML patients respond to monotherapy with a median duration of response of 8 months, suggesting that IDH1 inhibitors shoul...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
A ketogenic diet attenuates proliferation and stemness of glioma stem‑like cells by altering metabolism resulting in increased ROS production. Int J Oncol. 2019 Dec 13;: Authors: Ji CC, Hu YY, Cheng G, Liang L, Gao B, Ren YP, Liu JT, Cao XL, Zheng MH, Li SZ, Wan F, Han H, Fei Z Abstract Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Opinion statementMalignancies arising in midline brain structures, including lymphomas, teratomas, germinomas, diffuse midline gliomas, and medulloblastomas typically respond to systemic therapies, and excessive surgical excision can result in serious complications, so that total surgical removal is not routinely performed. Identifying tumor specific biomarkers that can facilitate diagnosis at early stage and allow for dynamic surveillance of the tumor is of great clinical importance. However, existing standard methods for biopsy of these brain neoplasms are high risk, time consuming, and costly. Thus, less invasive and mo...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
Abstract13N-Ammonia (13N-NH3) is widely used positron emission tomography/computed tomography (PET/CT) radiotracer for the measurement of myocardial blood perfusion; the possible role of13N-NH3 PET or PET/CT in oncological disease is not yet clear. Aim of this review is to evaluate the diagnostic performances of13N-NH3 PET in this field. A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted including articles up to June 2019. Eighteen articles were finally included in the review. From the analyses of the selected studies, the following main findings could be drawn: (1)...
Source: Japanese Journal of Radiology - Category: Radiology Source Type: research
ConclusionsDynamic contrast ‐enhanced‐Magnetic resonance imaging is a promising noninvasive imaging method that has moderate or high accuracy in stratifying gliomas. DCE‐MRI shows high diagnostic accuracy in discriminating between HGGs and their low‐grade counterparts, and moderate diagnostic accuracy in discriminating recurrent lesions and treatment‐related changes as well as PCNSLs and HGGs.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
ConclusionsAYA in the US experience disparities in cancer survival based on insurance status, independent of late stage of presentation. Patients age 26 ‐39 may be especially vulnerable to health outcomes associated with poor socioeconomic status, treatment disparities, and poor access to care.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Abstract Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and shown to play important roles in signaling and disease. Shcbp1 acts as Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-β1/Smad and β-catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphom...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
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Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
In this study, we further explored the role of let-7 in peripheral T cell homeostasis. We show that similar to Dicer-deficient mice, let-7-deficient animals develop severe peripheral T cell lymphopenia which appears to be a result of impaired survival due to the low expression of the pro-survival factor Bcl2. In addition, we demonstrate that let-7 controls Bcl2-mediated survival through an IL-7-independent mechanism. Results Peripheral T Cell Lymphopenia in Dicer-Deficient and Lin28Tg Mice Dicer ablation in T cells results in the reduction of mature CD4+ and CD8+ lymphocytes (26) suggesting that RNA interference may hav...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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