Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel

Bayat, Noushin; Ebrahimi‐Barough, Somayeh; Javidan, Abbas Norouzi; Saberi, Hooshang; Tajerian, Roksana; Ardakan, Mohammad Mehdi Mokhtari; Shirian, Sadegh; Ai, Arman; Ai, Jafar

doi:10.1016/j.biopha.2016.11.003

Cited by 51 publications

(76 citation statements)

References 54 publications

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“…The reduction in availability of downstream products of the mevalonate pathway is thought to be a key mechanism for the observed growth inhibiting effect of different statins on different cancer cell types including glioma cells [51][52][53][54][55][56][57][58]. Downstream products of the mevalonate pathway are important for prenylation (activation) of cellular proteins Ras, Rho, and Rac, which are small GTPases critical for regulation of cell growth and survival [51].…”

Section: Statins: Atorvastatin Lovastatin Simvastatin and Pravastatinmentioning

confidence: 99%

“…Downstream products of the mevalonate pathway are important for prenylation (activation) of cellular proteins Ras, Rho, and Rac, which are small GTPases critical for regulation of cell growth and survival [51]. Other proposed mechanisms include induction of apoptosis and inhibition of cell migration: Apoptosis may be induced by altering the cellular response to stress through the Jun N-terminal kinase (JNK)-dependent cell death pathway [59], by indirectly activating Caspase-3 [56,57], or by decreasing the expression of antiapoptotic proteins such as Bcl-2 and upregulating the expression of proapoptotic proteins such as Bax and Bim [52]. Cellular migration and invasion may be inhibited through inactivation of focal adhesion kinase (FAK) [60], or decreasing the amount of extracellular matrix-degrading enzymes and matrix metalloproteinases released from microglia into the glioma environment [61].…”

Section: Statins: Atorvastatin Lovastatin Simvastatin and Pravastatinmentioning

confidence: 99%

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In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Vasilev

Sofi

et al. 2018

Neuroglia

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Glioblastoma multiforme (GBM) is an extremely malignant type of brain cancer which originates from astrocytes or their precursors. Glioblastoma multiforme cells share some features with astrocytes but are characterized by highly unstable genomes with multiple driver mutations and aberrations. Effective therapies for GBM are lacking and hardly any progress has been made in the last 15 years in terms of improving the outcomes for patients. The lack of new especially targeted anti-GBM medications has prompted scientists in academia around the world to test whether any of the currently approved drugs might be used to fight this devastating disease. This approach is known as repurposing. Dozens of drugs have been reported to have anti-GBM properties in vitro but there is no solid evidence for the clinical efficacy of any of them. Perhaps the most interesting group of those repurposed are tricyclic antidepressants but the mechanism of their action on GBM cells remains obscure. In this brief review we consider various approaches to repurpose drugs for therapy of GBM and highlight their limitations. We also pay special attention to the mitochondria, which appear to be intimately involved in the process of apoptosis and could be a focus of future developments in search of a better treatment for patients suffering from GBM.

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Section: Statins: Atorvastatin Lovastatin Simvastatin and Pravastatinmentioning

confidence: 99%

Section: Statins: Atorvastatin Lovastatin Simvastatin and Pravastatinmentioning

confidence: 99%

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Vasilev

Sofi

et al. 2018

Neuroglia

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“…Simvastatin exerted its chemotherapeutic effect in HCC by inducing G0/G1 cell cycle arrest via a novel mechanism through which statins upregulate p21 and p27 by activating the AMPK pathway and inhibiting the signal transducer and activator of transcription factor 3 (STAT3)-Skp2 pathway, respectively 13 . Atorvastatin has been found to inhibit tumor growth and to induce apoptosis or autophagy in malignant tumors [14][15][16][17][18] . However, a few studies stated that atorvastatin could potentially modulate cellular senescence and reduce tumor formation in HCC 19 .…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway

et al. 2020

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Hepatocellular carcinoma (HCC), a hepatic malignancy, has a poor prognosis and contributes to cancer-related death worldwide. Cellular senescence is an anticancer therapeutic strategy that causes irreversible cell cycle arrest and enables immune-mediated clearance of cancer cells. Atorvastatin, an HMG-CoA reductase inhibitor, has been shown to inhibit tumor growth and induce apoptosis or autophagy in malignant tumors. However, whether atorvastatin can induce HCC cell senescence and the mechanisms involved are poorly understood. The effects of atorvastatin-induced senescence were examined in both HCC cells and mouse xenograft models. The phenomenon and mechanism of senescence were examined by cell cycle analysis, senescence-associated β-galactosidase (SA-β-gal) staining and western blotting in HCC cells, and HCC tissues from mice were analyzed by immunohistochemical (IHC) staining. We demonstrated that atorvastatin induced cell growth inhibition and G0/G1 phase cell cycle arrest, leading to senescence in HCC cells. Atorvastatin-induced senescence was independent of p53, p14, and p16, and atorvastatin not only decreased the secretion of IL-6, a major senescence-associated secretory phenotype (SASP) factor, and the phosphorylation of STAT3 but also inhibited the expression of hTERT, a catalytic subunit of telomerase. Supplementation with exogenous IL-6 reversed both atorvastatin-induced suppression of STAT3 phosphorylation and hTERT expression and atorvastatin-induced senescence. Overexpression of constitutively activated STAT3 rescued HCC cells from atorvastatin-induced hTERT suppression and senescence. Moreover, atorvastatin decreased tumor growth in mouse xenograft models. Consistent with these results, atorvastatin decreased the IL-6, p-STAT3, and hTERT levels and increased β-gal expression in tumor sections. Taken together, these data indicate that atorvastatin can induce atypical cellular senescence in HCC cells to inhibit tumor growth, an effect mediated by downregulation of hTERT through suppression of the IL-6/STAT3 pathway.

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“…Brain glioma is the most common primary tumor of the central nervous system, and one of the main causes of death in patients with intracranial tumors . The poor prognosis and high recurrence rate of glioma is largely due to the abundant blood flow, rapid growth, susceptibility of invasion to surrounding normal brain tissues and resistance to radiotherapy and chemotherapy .…”

Section: Introductionmentioning

confidence: 99%

“…Brain glioma is the most common primary tumor of the central nervous system, and one of the main causes of death in patients with intracranial tumors. [1][2][3][4] The poor prognosis and high recurrence rate of glioma is largely due to the abundant blood flow, rapid growth, susceptibility of invasion to surrounding normal brain tissues and resistance to radiotherapy and chemotherapy. [5][6][7][8] The tumorigenesis of glioma is biologically complex, involving a series of pathophysiological changes, and expression changes of many genes and signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

Zhu

Chen

et al. 2019

Intl Journal of Cancer

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Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA‐LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA‐LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR‐31‐5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR‐31‐5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR‐31‐5p‐RISC complex, and biotinylated miR‐31‐5p pull‐down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR‐31‐5p. Collectively, our study has identified a novel lncRNA‐LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.

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Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel

Cited by 51 publications

References 54 publications

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

In Search of a Breakthrough Therapy for Glioblastoma Multiforme

Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway

A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA

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