Rolipram potentiates bevacizumab-induced cell death in human glioblastoma stem-like cells

Ramezani, Sara; Vousooghi, Nasim; Kapourchali, Fatemeh Ramezani; Hadjighasem, Mahmoudreza; Hayat, Parisa; Amini, Naser; Joghataei, Mohammad Taghi

doi:10.1016/j.lfs.2017.02.005

Cited by 34 publications

(27 citation statements)

References 51 publications

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“…25 Here, we found that hypoxia accelerated VM EMT, the reversible dedifferentiation process of polarized epithelial cells, has been shown to play an important role in acquiring endothelial-like properties to form vessel-like structures in epithelial cancers. 35 Meng et al 36 44 Ramezani et al 45 demonstrated that human glioblastoma stem-like cells promoted themselves proliferation by secreting the VEGFA in an autocrine manner. Therefore, we inferred that VEGFA may affect VM by endowing SACC cells stemness.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Wang

Zheng

et al. 2019

Cell Proliferation

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Objectives To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved. Materials and methods Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT‐PCR were used to detect the effect of hypoxia on VE‐cadherin and VEGFA expression. And pro‐vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E‐cadherin, N‐cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF‐1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF‐1α level were analysed. Results Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE‐cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N‐cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E‐cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF‐1α expression. Conclusions VEGFA played an important role in hypoxia‐induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.

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Section: Discussionmentioning

confidence: 99%

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Wang

Zheng

et al. 2019

Cell Proliferation

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“…PDEs are negative regulators of intracellular cyclic nucleotide generation; dysregulated PDE expression has been observed in lung [4] and brain [5] tumor tissues, and found to be associated with unfavorable clinical prognosis. Notably, previous studies have shown that inhibition of PDEs leads to inhibition of cell proliferation or induction of apoptosis in NSCLC cells [6], glioblastoma stem-like cells [7], and diffuse large B-cell lymphoma cells [8]. These findings suggest that PDEs may be considered as an effective therapeutic target for NSCLC treatment.…”

Section: Introductionmentioning

confidence: 85%

A Novel Flavonoid Kushenol Z from Sophora flavescens Mediates mTOR Pathway by Inhibiting Phosphodiesterase and Akt Activity to Induce Apoptosis in Non-Small-Cell Lung Cancer Cells

et al. 2019

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The roots of Sophora flavescens (SF) are clinically used as a traditional Chinese medicine for the treatment of various lung diseases. In this study, we investigated the mechanism by which SF inhibits proliferation and induces apoptosis in non-small-cell lung cancer (NSCLC) cells. A new compound, kushenol Z (KZ), and 14 known flavonoids were isolated from SF. KZ, sophoraflavanone G, and kushenol A demonstrated potent cytotoxicity against NSCLC cells in a dose- and time-dependent manner; KZ showed a wide therapeutic window. We also found that KZ induced NSCLC cell apoptosis by increasing the Bax/Bcl-2 ratio and by activating caspase-3 and caspase-9 leading to mitochondrial apoptosis, and upregulated CHOP and activatedcaspase-7 and caspase-12, which triggered the endoplasmic reticulum stress pathway. After KZ treatment, we observed cAMP accumulation, which reflected the inhibition of cAMP-phosphodiesterase (PDE), along with the increase in PKA activity; additionally, phospho-p70 S6 kinase was downregulated. KZ also attenuated the phosphorylation of Akt and PRAS40, which was partially rescued by an Akt activator. This suggested that KZ mediated the antiproliferative activity in NSCLC cells by inhibiting the mTOR pathway through the inhibition of cAMP-PDE and Akt. These findings suggested that KZ may be used as a promising cAMP-PDE and Akt inhibitor in targeted chemotherapeutic drug development.

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“…A preclinical study (in vivo) on an animal model conducted by another research group in 2014 found that fluoxetine was bound to AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) which could induce Ca 2+ influx inside cells to overload the mitochondria and trigger apoptosis, in a similar effect to Temozolomide (17). In a study conducted by Ramezani et al on human glioblastoma stem-like cells and published in 2017, rolipram potentiated the effect of bevacizumab to kill cells with high expression of VEGF A (29). A nationwide study, conducted in Denmark in the form of a case-control study, showed that long-term use of TCAs could be associated with a lower risk of gliomas with an odds ratio (OR=0.72), but that did not reach statistical significance (28).…”

Section: D) Possible Cytotoxic Effectmentioning

confidence: 99%

Antidepressant prescriptions in neurosurgical practice: a survey of current trends

Bayoumi

Efe²,

Öztürk³

et al. 2018

Turkish Neurosurgery

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AIM: To better understand the indications and the impact of antidepressant drugs on the field of neurosurgery in terms of risks and benefits in Turkey. MATERIAL and METHODS: A national survey was conducted among neurosurgeons in current practice in Turkey to report routine prescription trends of antidepressant drugs. Gender, neurosurgical subspecialty, city, type of practice, years of experience, antidepressant agent, indications and reasons not to prescribe were ascertained. A brief review of literature was done to show clinical and research evidence. RESULTS: A total of 336 neurosurgeons took the survey; 53% of them prescribe antidepressants routinely, whereas 47% of them do not. Of the 72% non-prescribers prefer to refer their patients to a psychiatrist and 22% of them believe that antidepressants have no role in neurosurgery. Vascular and pediatric neurosurgeons as well as neurosurgeons at research hospitals showed the lowest prescription proportion, while general and brain tumor neurosurgeons and ones in private practice showed the highest prescription proportion. Surgeons with more than 20 year-experience had the lowest prescription proportion (43%). Type of practice and years of experience showed a statistically significant association with the prescription of antidepressant drugs across (p=0.002 and p=0.025, respectively). CONCLUSION: Type of practice and years of experience showed a statistically significant association with the proportion of antidepressants' prescribers in Turkish neurosurgery practice at the time of this survey. Non-prescriber neurosurgeons need to recognize the indications, whereas prescribers have to understand the risks of using antidepressants.

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Rolipram potentiates bevacizumab-induced cell death in human glioblastoma stem-like cells

Abstract: This study highlighted a booster cytotoxic effect of combined rolipram and bevacizumab treatment on the GCSCs primary culture, suggesting that this approach is warranted in treatment of GBMs overexpressing VEGF and PDE4A.

Cited by 34 publications

References 51 publications

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

A Novel Flavonoid Kushenol Z from Sophora flavescens Mediates mTOR Pathway by Inhibiting Phosphodiesterase and Akt Activity to Induce Apoptosis in Non-Small-Cell Lung Cancer Cells

Antidepressant prescriptions in neurosurgical practice: a survey of current trends

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