The eIF4A Inhibitor Silvestrol Blocks the Growth of Human Glioblastoma Cells by Inhibiting AKT/mTOR and ERK1/2 Signaling Pathway

Zhang, Wei; Gong, Pian; Tian, Qi; Han, Shoumeng; Wang, Jianfeng; He, Peibang; Guo, Yujia; Wang, Guijun; Chen, Qianxue; Huang, Jie; Li, Mingchang

doi:10.1155/2022/4396316

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…A large amount of data has accumulated since the first evidences for the existence of cancer stem cells in GBM and GS were published [22,23,63,64] (for overview, see, [24,25]). On the basis of the first reports, many researchers utilized CD133-positive GBM cells in their experiments, others used established cell lines such as U87 or U251 (e.g., [32,[65][66][67]). The situation is further complicated by the intertumor and intratumor heterogeneity of GBMs [15][16][17][18][19][20][21] and the possible impact of the cell origin on therapy sensitivity [37].…”

Section: Discussionmentioning

confidence: 99%

Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma

Zechel,

Loy,

Wegner

et al. 2024

PLoS ONE

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Glioblastoma multiforme (GBM) and the GBM variant gliosarcoma (GS) are among the tumors with the highest morbidity and mortality, providing only palliation. Stem-like glioma cells (SLGCs) are involved in tumor initiation, progression, therapy resistance, and relapse. The identification of general features of SLGCs could contribute to the development of more efficient therapies. Commercially available protein arrays were used to determine the cell surface signature of eight SLGC lines from GBMs, one SLGC line obtained from a xenotransplanted GBM-derived SLGC line, and three SLGC lines from GSs. By means of non-negative matrix factorization expression metaprofiles were calculated. Using the cophenetic correlation coefficient (CCC) five metaprofiles (MPs) were identified, which are characterized by specific combinations of 7–12 factors. Furthermore, the expression of several factors, that are associated with GBM prognosis, GBM subtypes, SLGC differentiation stages, or neural identity was evaluated. The investigation encompassed 24 distinct SLGC lines, four of which were derived from xenotransplanted SLGCs, and included the SLGC lines characterized by the metaprofiles. It turned out that all SLGC lines expressed the epidermal growth factor EGFR and EGFR ligands, often in the presence of additional receptor tyrosine kinases. Moreover, all SLGC lines displayed a neural signature and the IDH1 wildtype, but differed in their p53 and PTEN status. Pearson Correlation analysis identified a positive association between the pluripotency factor Sox2 and the expression of FABP7, Musashi, CD133, GFAP, but not with MGMT or Hif1α. Spherical growth, however, was positively correlated with high levels of Hif1α, CDK4, PTEN, and PDGFRβ, whereas correlations with stemness factors or MGMT (MGMT expression and promoter methylation) were low or missing. Factors highly expressed by all SLGC lines, irrespective of their degree of stemness and growth behavior, are Cathepsin-D, CD99, EMMPRIN/CD147, Intβ1, the Galectins 3 and 3b, and N-Cadherin.

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Section: Discussionmentioning

confidence: 99%

Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma

Zechel,

Loy,

Wegner

et al. 2024

PLoS ONE

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“…Silvestrol is an eIF4A inhibitor able to kill tumor cells in colorectal carcinoma, acute lymphoblastic leukemia, breast, and prostate cancer in mice and human cells ( Figure 7C ) ( Cencic et al, 2009 ; Alachkar et al, 2013 ; Kogure et al, 2013 ). Interestingly, Silvestrol exerts antitumor effects in U251 and U-87 MG GB cells by inhibiting the expression of Cyclin D1, the PI3K/AKT/mTOR, and ERK1/2 signaling cascades ( Zhang et al, 2022 ) ( Figure 7C ). Currently, the molecular mechanism underlying these observations are not well understood.…”

Section: New Drugs Targeting Translation In Gbmentioning

confidence: 99%

The dark side of mRNA translation and the translation machinery in glioblastoma

Montiel-Dávalos

Ayala²,

Hernández³

2023

Front. Cell Dev. Biol.

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Among the different types of cancer affecting the central nervous system (CNS), glioblastoma (GB) is classified by the World Health Organization (WHO) as the most common and aggressive CNS cancer in adults. GB incidence is more frequent among persons aged 45–55 years old. GB treatments are based on tumor resection, radiation, and chemotherapies. The current development of novel molecular biomarkers (MB) has led to a more accurate prediction of GB progression. Moreover, clinical, epidemiological, and experimental studies have established genetic variants consistently associated with the risk of suffering GB. However, despite the advances in these fields, the survival expectancy of GB patients is still shorter than 2 years. Thus, fundamental processes inducing tumor onset and progression remain to be elucidated. In recent years, mRNA translation has been in the spotlight, as its dysregulation is emerging as a key cause of GB. In particular, the initiation phase of translation is most involved in this process. Among the crucial events, the machinery performing this phase undergoes a reconfiguration under the hypoxic conditions in the tumor microenvironment. In addition, ribosomal proteins (RPs) have been reported to play translation-independent roles in GB development. This review focuses on the research elucidating the tight relationship between translation initiation, the translation machinery, and GB. We also summarize the state-of-the-art drugs targeting the translation machinery to improve patients’ survival. Overall, the recent advances in this field are shedding new light on the dark side of translation in GB.

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“…In contrast, mTORC1 activation is inhibited to stop the downstream pathways, which in turn prevent protein synthesis, cell growth, and metabolism (Figure 1). 29,39,42 This plays an important role in the treatment of many EBV‐associated cancers 34 …”

Section: Latent Membrane Proteinsmentioning

confidence: 99%

Targeting EBV‐encoded products: Implications for drug development in EBV‐associated diseases

Lv,

Ding,

Zhang

et al. 2023

Reviews in Medical Virology

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Epstein‐Barr virus, a human gamma‐herpesvirus, has a close connection to the pathogenesis of cancers and other diseases, which are a burden for public health worldwide. So far, several drugs or biomolecules have been discovered that can target EBV‐encoded products for treatment, such as Silvestrol, affinity toxin, roscovitine, H20, H31, curcumin, thymoquinone, and ribosomal protein L22. These drugs activate or inhibit the function of some biomolecules, affecting subsequent signalling pathways by acting on the products of EBV. These drugs usually target LMP1, LMP2; EBNA1, EBNA2, EBNA3; EBER1, EBER2; Bam‐HI A rightward transcript and BHRF1. Additionally, some promising findings in the fields of vaccines, immunological, and cellular therapies have been established. In this review, we mainly summarise the function of drugs mentioned above and unique mechanisms, hoping that we can help giving insight to the design of drugs for the treatment of EBV‐associated diseases.

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The eIF4A Inhibitor Silvestrol Blocks the Growth of Human Glioblastoma Cells by Inhibiting AKT/mTOR and ERK1/2 Signaling Pathway

Cited by 7 publications

References 22 publications

Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma

Molecular signature of stem-like glioma cells (SLGCs) from human glioblastoma and gliosarcoma

The dark side of mRNA translation and the translation machinery in glioblastoma

Targeting EBV‐encoded products: Implications for drug development in EBV‐associated diseases

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