scholarly journals Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition

2021 ◽  
Vol 22 (18) ◽  
pp. 9665
Author(s):  
Liliya Kopanitsa ◽  
Maksym V. Kopanitsa ◽  
Dewi Safitri ◽  
Graham Ladds ◽  
David S. Bailey
Keyword(s):  
Cell Proliferation ◽  
Multidrug Resistance ◽  
Pde5 Inhibitor ◽  
Chemotherapeutic Agents ◽  
New Combination ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Pde Inhibitors ◽  
Novel Approaches ◽  
Pde Inhibition

The paucity of currently available therapies for glioblastoma multiforme requires novel approaches to the treatment of this brain tumour. Disrupting cyclic nucleotide-signalling through phosphodiesterase (PDE) inhibition may be a promising way of suppressing glioblastoma growth. Here, we examined the effects of 28 PDE inhibitors, covering all the major PDE classes, on the proliferation of the human U87MG, A172 and T98G glioblastoma cells. The PDE10A inhibitors PF-2545920, PQ10 and papaverine, the PDE3/4 inhibitor trequinsin and the putative PDE5 inhibitor MY-5445 potently decreased glioblastoma cell proliferation. The synergistic suppression of glioblastoma cell proliferation was achieved by combining PF-2545920 and MY-5445. Furthermore, a co-incubation with drugs that block the activity of the multidrug resistance-associated protein 1 (MRP1) augmented these effects. In particular, a combination comprising the MRP1 inhibitor reversan, PF-2545920 and MY-5445, all at low micromolar concentrations, afforded nearly complete inhibition of glioblastoma cell growth. Thus, the potent suppression of glioblastoma cell viability may be achieved by combining MRP1 inhibitors with PDE inhibitors at a lower toxicity than that of the standard chemotherapeutic agents, thereby providing a new combination therapy for this challenging malignancy.

scholarly journals Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1

2020 ◽  
Author(s):  
Yihao Zhu ◽  
Handong Wang ◽  
Maoxing Fei ◽  
Ting Tang ◽  
Wenhao Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
High Grade Glioma ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Protein Levels ◽  
Enhanced Expression ◽  
Human Glioblastoma Cells ◽  
Glioblastoma Cell Lines

AbstractSmarcd1 is a component of an evolutionary conserved chromatin remodeling complex—SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferation and tumorigenicity. However, the inhibitory role of Smarcd1 in human glioblastoma cells has not been well illustrated. Both U87 and U251 human glioblastoma cell lines were employed in the present study. The lentivirus-mediated gene knockdown and overexpression approach was conducted to determine the function of Smarcd1. The protein levels were tested by western blot, and the relative mRNA contents were detected by quantitative real-time PCR. Cell viability was tested by CCK-8 and colony-forming assay. Transwell assays were utilized to evaluate the motility and invasive ability. Flow cytometry was employed to analyze cell cycle and apoptosis. SPSS software was used for statistical analysis. Low expression of Smarcd1 was observed in glioblastoma cell lines and in patients with high-grade glioma. Importantly, the depletion of Smarcd1 promoted cell proliferation, invasion, and chemoresistance, whereas enhanced expression of Smarcd1 inhibited tumor-malignant phenotypes. Mechanistic research demonstrated that overexpression of Smarcd1 decreased the expression of Notch1, while knockdown of Notch1 increased the expression of Smarcd1 through Hes1 suppression. Hence, the crosstalk between Smarcd1 and Notch1, which formed a feedback loop, was crucial in regulation of glioblastoma malignant phenotypes. Furthermore, targeting Smarcd1 could be a potential strategy for human glioblastoma treatment.

scholarly journals SNHG9/miR-199a-5p/Wnt2 Axis Regulates Cell Growth and Aerobic Glycolysis in Glioblastoma

2019 ◽  
Vol 78 (10) ◽  
pp. 939-948 ◽  
Author(s):  
Han Zhang ◽  
Danxia Qin ◽  
Zhixian Jiang ◽  
Jinning Zhang
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Mrna Expression ◽  
Cell Lines ◽  
Aerobic Glycolysis ◽  
Stress Test ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Qrt Pcr ◽  
Glioblastoma Cell Lines

Abstract Aerobic glycolysis is a characteristic in cancers that is important for cancer cell proliferation. Emerging evidence shows that long non-coding RNA (LncRNA) participates in glucose metabolism and cell proliferation in cancer. This study explored the effect of LncRNA: SNHG9 in glioblastoma. The mRNA expression of SNHG9 in human glioma tissues and glioblastoma cell lines was measured by qRT-PCR. Glioblastoma cell lines (U87 and U251) were transfected with miR-199a-5p or SNHG9-expressing plasmid and cell viability as well as concentrations of glucose and lactate were measured. The extracellular acidification was evaluated by glycolysis stress test. The Wnt2 levels were determined by qRT-PCR and Western blot. Results showed that the mRNA expression of SNHG9 was elevated in glioblastoma tissues. The elevated SNHG9 expression was related to lower survival rate in patients with glioma. SNHG9 could downregulate miR-199a-5p and upregulate Wnt2 in glioblastoma cells. Overexpression of SNHG9 in glioblastoma cells promoted aerobic glycolysis and cell proliferation, which could be attenuated by miR-199a-5p. Results of this study indicated an effect of SNHG9/miR-199a-5p/Wnt2 axis in regulating cell growth and aerobic glycolysis in glioblastoma.

Effects of different alcoholic beverages on human glioblastoma cell lines

2021 ◽  
Vol 17 ◽  
Author(s):  
Sumbla Sheikh ◽  
Alexander Sturzu ◽  
Thomas Nägele ◽  
Ulrike Ernemann ◽  
Stefan Heckl
Keyword(s):  
Cell Proliferation ◽  
White Wine ◽  
Alcoholic Beverages ◽  
Membrane Disruption ◽  
Glioblastoma Cell ◽  
Proliferation Inhibition ◽  
Red Wines ◽  
Glioblastoma Cells ◽  
Glioblastoma Cell Lines

Background: Anecdotal reports from neurosurgeons suggested that patients with glioblastoma who consumed a moderate amount of alcoholic beverages after glioblastoma surgery presented with improved vitality. Objective: This study aimed to investigate that if any evidence for these anecdotal reports can be reproduced experimentally. We also studied the effects of different alcoholic beverages on glioblastoma cells. Methods: GOS-3 glioblastoma cells and PC3 prostate carcinoma cells as control were incubated with beer, red wine, white wine, vodka, and whiskey at different concentrations. Membrane disruption by acute cytotoxicity and apoptosis induction was evaluated via Annexin-V-FITC flow cytometry and confocal laser scanning microscopy. Long-term effects on cell proliferation were studied by the XTT test. Results: There was no increase in membrane disruption even at physiologically high alcohol concentrations of 1 ‰. Cell proliferation was significantly inhibited by vodka and beer. Among the wines, the white wine caused slight proliferation inhibition in GOS-3 glioblastoma cells while inducing slightly enhanced proliferation in PC3 prostate cancer cells. After these results, more different brands of vodka and additional white and red wines from different grapes were used. While confirming the initial results, no additional differences between the different brands of vodka were observed. In the wine investigations, all the wines showed cell proliferation inhibition during long-term incubation of three different glioblastoma cell lines. Consistently, the inhibition from red wines was lower than the inhibition from white and rosé wines. Conclusion: In conclusion, alcoholic beverages at different concentrations used during the ingestion have both cytotoxic and antiproliferative effects on glioblastoma cells in vitro which could not be found in the controls with pure ethanol.

Combination Therapy of Cisplatin and Other Agents for Osteosarcoma: A Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Mohamad Zahid Kasiram ◽  
Hermizi Hapidin ◽  
Hasmah Abdullah ◽  
Azlina Ahmad ◽  
Sarina Sulong
Keyword(s):  
Radiation Therapy ◽  
Survival Rate ◽  
Chemotherapeutic Agents ◽  
New Combination ◽  
Rapid Progression ◽  
Combination Regimen ◽  
Chemotherapeutic Drugs ◽  
Primary Bone Tumor ◽  
Phytochemical Compounds

Background: Osteosarcoma is the most common type of primary bone tumor in children and adolescents, which is associated with rapid progression and poor prognosis. Multimodal therapy is the most common approach utilized for osteosarcoma management, such as the application of chemotherapy in combination with surgery or radiation therapy. Cisplatin is one of the predominantly used chemotherapeutic agents for osteosarcoma. Optimally, it is employed in combination with other chemotherapeutic drugs along with surgery or radiation therapy. Despite the availability of numerous treatment approaches, patient survival rate has not definitively improved over the past three decades. Methods: We summarized all findings regarding the combination of cisplatin with other chemotherapeutic agents as well as with phytochemical compounds. Results: A combination of cisplatin with phytochemical compound synergistically enhances the killing effect of cisplatin on osteosarcoma cells with fewer side effects compared to combination with other chemotherapeutic agents. Conclusion: Conclusively, a combination of cisplatin with selected chemotherapeutic drugs, has been shown to be effective. However, the unchanged survival rate urges for the search of a new combination regimen. As a collaborative effort to substantiate the therapeutic efficacy, the combination with phytochemical compounds shows a promising response both in vitro as well as in the preclinical study.

Role Of Cyclic Amp In The Inhibition Of Human Platelet Functions By Quercetin, A Flav0N0Id That Potentiates PGI2 Effect

1981 ◽  
Author(s):  
J P Cazenave ◽  
A Beretz ◽  
A Stierlé ◽  
R Anton
Keyword(s):  
Maximum Level ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Pde Inhibitors ◽  
Pde Inhibition ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Dose Dependent

Injury to the endothelium (END) and subsequent platelet (PLAT)interactions with the subEND are important steps in thrombosis and atherosclerosis. Thus,drugs that protect the END from injury and also inhibit PLAT function are of interest. It has been shown that some flavonoids(FLA), a group of compounds found in plants, prevent END desquamation in vivo, inhibit cyclic nucleotide phosphodiesterases(PDE)and inhibit PLAT function. We have studied the structure-activity relationships of 13 purified FLA on aggregation and secretion of 14c-5HT of prelabeled washed human PLAT induced by ADP, collagen(COLL) and thrombin(THR). All the FLA were inhibitors of the 3 agents tested. Quercetin(Q), was the second best after fisetin. It inhibited secretion and aggregation with I50 of 330µM against 0.1 U/ML.THR, 102µM against 5µM ADP and 40 µM against COLL. This inhibitory effect is in the range of that of other PDE inhibitors like dipyridamole or 3-isobutyl-l- methylxanthine. The aggregation induced by ADP, COLL and THR is at least mediated by 3 mechanisms that can be inhibited by increasing cAMP levels. We next investigated if Q, which is a PDE inhibitor of bovine aortic microsomes,raises PLAT cAMP levels. cAMP was measured by a protein-binding method. ADP- induced aggregation(5µM) was inhibited by PGI2 (0.1 and 0.5 nM) . Inhibition was further potentiated(l.7 and 3.3 times) by lOµM Q, which alone has no effect on aggregation. The basal level of cAMP(2.2 pmol/108PLAT) was not modified by Q (50 to 500µM). Using these concentrations of Q,the rise in cAMP caused by PGI2(0.1 and 0.5nM) was potentiated in a dose dependent manner. Q potentiated the effect of PGI2 on the maximum level of cAMP and retarded its breakdown. Thus Q and possibly other FLA could inhibit the interaction of PLAT with the components of the vessel wall by preventing END damage and by inhibiting PLAT function through a rise in cAMP secondary to PDE inhibition and potentiation of the effect of vascular PGI2 on PLAT adenylate cyclase.

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