Interference with distinct steps of sphingolipid synthesis and signaling attenuates proliferation of U87MG glioma cells

Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea; Nusshold, Christoph; Brunner, Anna; Plastira, Ioanna; Rechberger, Gerald; Reicher, Helga; Wadsack, Christian; Zimmer, Andreas; Malle, Ernst; Sattler, Wolfgang

doi:10.1016/j.bcp.2015.05.007

Cited by 34 publications

(42 citation statements)

References 69 publications

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“…In addition, it has been reported that the inhibition of sphingolipids by myriocin in glioma cells attenuates proliferation (Bernhart et al 2015). Our results are in line with these observations, suggesting an important role for sphingolipids in cell cycle progression.…”

Section: Figuresupporting

confidence: 92%

Sphingolipid synthesis and role in uterine epithelia proliferation

Cerbón¹,

Baranda-Ávila²,

Falcón-Muñoz³

et al. 2018

Reproduction

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Sphingolipids are involved in the regulation of cell proliferation. It has been reported that diacylglycerol and sphingosine-1-phosphate generation, during the synthesis of phospho-sphingolipids, is necessary for both, G1-S transition of cell cycle during the sustained activation of protein kinase C in various cell models (MDCK, and) and AKT pathway activation. During the estrous cycle of the rat, AKT signaling is the main pathway involved in the regulation of uterine cell proliferation. The aim of the present study was to investigate the role of sphingolipid synthesis during proliferation of uterine cells in the estrous cycle of the rat. On metestrus day, when both luminal and glandular uterine epithelia present the maximal BrdU-labeled cells (S phase cells), there was an increase in the relative abundance of total sphingomyelins, as compared to estrus day. Myriocin, a sphingolipid synthesis inhibitor administered on estrus day, before the new cell cycle of epithelial cells is initiated, decreased the abundance of sphingomyelin, accompanied by proliferation arrest in uterine epithelial cells on metestrus day. In order to study the sphingolipid signaling pathway affected by myriocin, we evaluated the activation of the PKC-AKT-GSK3b-Cyclin D3 pathway. We observed that total and phosphorylated protein kinase C diminished in uterine epithelial cells of myriocin treated animals. Interestingly, cyclin D3 nuclear localization was blocked by myriocin, concomitantly with a decrease in nuclear pRb expression. In conclusion, we demonstrate that sphingolipid synthesis and signaling are involved in uterine epithelial cell proliferation during the estrous cycle of the rat.

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Section: Figuresupporting

confidence: 92%

Sphingolipid synthesis and role in uterine epithelia proliferation

Cerbón¹,

Baranda-Ávila²,

Falcón-Muñoz³

et al. 2018

Reproduction

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“…Conversely, statins have been previously reported to prolong the survival and decrease the incidence of patients with various cancers (30)(31)(32). The mechanism of the anticancer activity of statins remains unclear, but a previous review has demonstrated this anticancer effect (33). Mitogen-activated protein kinase and extracellular signal-regulated kinase upregulate antiapoptotic molecules in small cell lung cancer (SCLC) cells (34,35), and simvastatin Table III.…”

Section: Discussionmentioning

confidence: 99%

“…A number of previous in vitro studies have demonstrated that statins arrest cells in the G1 or S phase by affecting cell-cycle regulatory proteins such as cyclins, cyclin-dependent kinases (CDKs), and inhibitors of CDK (33,41,42). In addition, statins have been considered to lead to apoptosis of cancer cells through effects of various molecules such as B cell lymphoma (Bcl)-2, Bcl-2-associated X protein and caspase 3 (33,(43)(44)(45). Furthermore, statins have been demonstrated to inhibit intracellular signaling pathways in cancer cells (33).…”

Section: Univariate Analysismentioning

confidence: 99%

“…In addition, statins have been considered to lead to apoptosis of cancer cells through effects of various molecules such as B cell lymphoma (Bcl)-2, Bcl-2-associated X protein and caspase 3 (33,(43)(44)(45). Furthermore, statins have been demonstrated to inhibit intracellular signaling pathways in cancer cells (33). Other studies have reported that statins activated anticancer immunity and may reduce the development of cancer cells and metastasis (46,47).…”

Section: Univariate Analysismentioning

confidence: 99%

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Statins improve survival in patients previously treated with nivolumab for advanced non‑small cell lung cancer: An observational study

et al. 2018

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There are a number of suggested predictive factors of nivolumab for non-small cell lung cancer (NSCLC), however, there is not enough evidence to determine a single factor that can predict the efficacy of nivolumab. As the progress of biomarkers for cancer treatment is improving, it has been speculated that certain clinical factors serve an important role when predicting the outcome of chemotherapy. A total of 67 patients treated with nivolumab for NSCLC from 2016-2017 were prospectively investigated. Age, sex, the Eastern Cooperative Oncology Group Performance Status, histology, epidermal growth factor receptor (EGFR) mutation, history of chemotherapy, smoking status, use of statins, use of fibrates, use of dipeptidyl peptidase-4 (DPP-4) inhibitors, and use of metformin were examined as clinical factors. Statistical analyses were performed using the Kaplan-Meier method and Cox regression adjusted for risk factors and the tumor response of 67 patients was assessed. The patients had a median age of 67 years (range, 36-87 years), and 46 males and 21 females were enrolled; performance status 0/1 was 59. Cases were categorized as adenocarcinoma (n=41), squamous cell carcinoma (n=17) and other (n=9). A total of 13 patients (19.4%) had EGFR mutations. These clinical factors were not statistically significant in overall survival (OS). Clinical laboratory findings, complications and use of medical agents including antidiabetes mellitus or lipidemia were also analyzed. Statins exhibited statistical significance for response (P= 0.02). Time-to-treatment failure (TTF) in statin-use group was not reached [95% confidence interval (CI): 1.9-not reached] and was 4.0 months (95% CI: 2.0-5.4) in the non-statin group (P=0.039). The median OS in statin-use group was not reached (95% CI: 8.7-not reached) and was 16.5 months (95% CI: 7.5-not reached) in the non-statin group (P= 0.058). NSCLC patients previously treated with nivolumab who were administered statins exhibited an increased response rate and longer TTF. This response was not statistically significant in OS.

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“…Erre mutatunk be néhány példát az 1. táblázatban [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

Section: öSszefoglaló Közleményunclassified

A vér–agy gát működése, öregedése és diszfunkciója. Átjutás a barrieren

Hutka

Dénès

2016

Orvosi Hetilap

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Az agy és a keringés kapcsolatát biztosító, mikroerek szintjén megjelenő védelmi vonal a vér-agy gát, amely az idegrendszer homeosztázisának fenntartásában, az agy védelmében, táplálásában és finoman regulált működésének biztosításában játszik jelentős szerepet. Funkcióját számos sejttípus összehangolt működése és molekuláris rendszerek szabályozott kifejeződése teszi lehetővé. Azonban ez a komplex rendszer bizonyos behatásokra károsodik, szerkezete megbomlik, s akkor a védelmi struktúra permeabilitása megnő. Ez nemkívánatos exogén és endogén anyagok idegrendszeri megjelenését vagy szintjének emelkedését eredményezi, amely számos akut és krónikus központi idegrendszeri betegség patomechanizmusában játszik szerepet. A vér-agy gát károsodásának legfőbb rizikófaktora maga az öregedés, amely DNS-mutáción, oxidatív károsodáson és gyulladásos mediátorok megjelenésén keresztül destrukturálja a védelmi rendszert. Ez bizonyos fokig a természetes öregedés velejárója, de a membrántranszporterek műkö-désének diszfunkciója patológiás állapotok kialakulásához is vezethet, amely a krónikus neurodegeneratív betegségek oki tényezői között szerepel. Ebben a közleményben a vér-agy gát felépítését, működését, károsodását és az agyi gyógyszerbeviteli lehetőségeket foglaljuk össze. Orv. Hetil., 2016, 157(51), 2019-2027. Kulcsszavak: vér-agy gát, membrántranszporterek, öregedés, gyógyszerátvitel a vér-agy gáton Function, aging and dysfunction of blood-brain barrier. Crossing the barrierThe blood-brain barrier is an interface between the circulation and brain. It is responsible for the homeostasis of central nervous system, protection and feeding of the brain and for providing the conditions for fine regulation of neurons. The coordinated function of different cell types and the regulated expression of molecular systems make possible the functionality of blood-brain barrier. However, this complex system can be broken due to different insults with a consequence of appearance of elevated levels of unwanted exogenous and endogenous molecules in the brain involved in the pathomechanisms of several disorders. The most important risk factor for the damage of blood-brain barrier is the aging itself, which causes disruption of the barrier through DNA mutation, oxidative stress and release of inflammatory mediators. Although the physiological aging is accompanied by morphological changes, the dysfunction of membrane transporters could also lead to neurodegenerative disorders. Structure, function and breakdown of the blood-brain barrier and the possibilities to cross it, are presented.Keywords: blood-brain barrier, membrane transporter proteins, aging, drug delivery , F., Hutka, B., Dénes, L. [Function, aging and dysfunction of blood-brain barrier. Crossing the barrier]. Orv. Hetil., 2016, 157(51), 2019-2027. (Beérkezett: 2016 elfogadva: 2016. Rövidítések Ang-1 = angiopoetin-1, a vascularis növekedési faktorok egyik típusa, az embrionális fejlődésben van szerepe; AQP-4 = aquaporin-4, membránprotein, amely a vízmolekulákat átvezeti a membrá...

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Interference with distinct steps of sphingolipid synthesis and signaling attenuates proliferation of U87MG glioma cells

Abstract: Graphical abstract

Cited by 34 publications

References 69 publications

Sphingolipid synthesis and role in uterine epithelia proliferation

Sphingolipid synthesis and role in uterine epithelia proliferation

Statins improve survival in patients previously treated with nivolumab for advanced non‑small cell lung cancer: An observational study

A vér–agy gát működése, öregedése és diszfunkciója. Átjutás a barrieren

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