scholarly journals Artificial microenvironment of in vitro glioblastoma cell cultures changes profile of miRNAs related to tumor drug resistance

2019 ◽  
Vol Volume 12 ◽  
pp. 3905-3918
Author(s):  
Monika Witusik-Perkowska ◽  
Magdalena Zakrzewska ◽  
Dariusz Jaskolski ◽  
Paweł P Liberski ◽  
Janusz Szemraj
Keyword(s):  
Drug Resistance ◽  
Cell Cultures ◽  
Glioblastoma Cell ◽  
Tumor Drug Resistance

Delivery and cytotoxicity of doxorubicin and temozolomide to primary glioblastoma cells using gold nanospheres and gold nanorods

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Jyoti Verma ◽  
Henk A. Van Veen ◽  
Sumit Lal ◽  
Cornelis J.F. Van Noorden
Keyword(s):  
Gold Nanoparticles ◽  
Cell Cultures ◽  
Gold Nanorods ◽  
Silica Coating ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Gold Nanospheres ◽  
Primary Glioblastoma ◽  
Direct Delivery

AbstractNanoparticles with coating entrapping a chemotherapeutic drug for delivery have not been tested for their cytotoxic effects in in-vitro glioblastoma cell cultures to increase treatment efficacy. Therefore, we synthesized silica-coated gold nanorods and gold nanospheres that were loaded with doxorubicin or temozolomide. The morphology of the nanoparticles was characterized using transmission electron microscopy (TEM), the molecular structure was characterized using infrared spectroscopy and in vitro efficacy was determined using glioblastoma cell cultures. TEM analysis showed that gold nanorods had a length of 49–65 nm and a diameter of 8.5–14 nm whereas gold nanospheres had a diameter of 9.5–37 nm. Infrared spectroscopy of doxorubicin and temozolomide and the silica coating revealed molecular fingerprints such as bending, stretching and vibrations of chemical bonds that confirmed the presence of silica coating and drug loading of the gold nanoparticles. In the biological assessment of the effects of drug-loaded gold nanoparticles on primary glioblastoma cell cultures, cytotoxicity, viability and the ratio of cyototoxicity and viability were used as parameters to analyze the effects on the cells of drug delivery via gold nanoparticles on the cells. Our data suggest that doxorubicin in the concentration range of 0.12–3.16 μM when delivered using both gold nanorods and nanospheres induced a 3.8–5.5-fold increased cytotoxicity in comparison to direct delivery. Temozolomide in the concentration range of 4.6–115 μM when delivered by either type of gold nanoparticles induced a 2–4-fold increased cytotoxicity in comparison to direct delivery. Nanospheres were more effective in delivery and cytotoxicity of doxorubicin and temozolomide to glioblastoma cells than gold nanorods. Our data suggest that gold nanoparticles and in particular gold nanospheres are more effective in delivery of doxorubicin and temozolomide to primary glioblastoma cells in culture than direct delivery.

scholarly journals Inhibiting adenine synthesis attenuates glioblastoma cell stemness and temozolomide resistance

2021 ◽  
Author(s):  
Simranjit X. Singh ◽  
Rui Yang ◽  
Kristen Roso ◽  
Landon J. Hansen ◽  
Changzheng Du ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mitochondrial Function ◽  
Brain Cancer ◽  
De Novo ◽  
Critical Role ◽  
Glioblastoma Cell ◽  
Respiratory Capacity ◽  
Complementary Approach

Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in adenine salvage, we demonstrate that transient adenine blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo adenine synthesis, attenuates stemness of MTAP-deficient GBM cells. This ALA-induced reduction in stemness is accompanied by compromised mitochondrial function, highlighted by diminished spare respiratory capacity. Direct pharmacological inhibition of mitochondrial respiration recapitulates the effect of ALA on GBM cell stemness, suggesting ALA targets stemness partially via affecting mitochondrial function. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ) in vitro and in an orthotopic GBM model. Collectively, these results identify critical roles of adenine supply in maintaining mitochondrial function and stemness of GBM cells, highlight a critical role of mitochondrial function in sustaining GBM stemness, and implicate adenine synthesis inhibition as a complementary approach for treating MTAP-deleted GBMs.

In Vitro Effects of Cocaine on Tunneling Nanotube Formation and Extracellular Vesicle Release in Glioblastoma Cell Cultures

2014 ◽  
Vol 55 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Chiara Carone ◽  
Susanna Genedani ◽  
Giuseppina Leo ◽  
Monica Filaferro ◽  
Kjell Fuxe ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Extracellular Vesicle ◽  
Glioblastoma Cell ◽  
Vesicle Release ◽  
Tunneling Nanotube ◽  
In Vitro Effects

A semisynthetic taxane Yg-3-46a effectively evades P-glycoprotein and β-III tubulin mediated tumor drug resistance in vitro

2013 ◽  
Vol 341 (2) ◽  
pp. 214-223 ◽  
Author(s):  
Pei Cai ◽  
Peihua Lu ◽  
Frances J. Sharom ◽  
Wei-Shuo Fang
Keyword(s):  
Drug Resistance ◽  
P Glycoprotein ◽  
Tumor Drug Resistance

Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy

1996 ◽  
Vol 84 (5) ◽  
pp. 839-845 ◽  
Author(s):  
Nobusada Shinoura ◽  
Lin Chen ◽  
Maqsood A. Wani ◽  
Young Gyu Kim ◽  
Jeffrey J. Larson ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Brain Tumors ◽  
Gap Junctions ◽  
Gap Junction ◽  
Cell Cultures ◽  
Messenger Rna ◽  
Bystander Effect ◽  
Glioblastoma Cell ◽  
Glioblastoma Cell Lines

✓ The expression of connexin43, the primary gap-junction constituent of glial cells, was evaluated at the messenger RNA and protein levels in different grades of astrocytoma to investigate the relevance of gap junctions in herpes simplex virus—thymidine kinase (HSV-tk)—mediated gene therapy of brain tumors. Transduction of the retroviral-mediated HSV-tk gene into tumor cells with subsequent administration of ganciclovir has recently been used as an experimental therapeutic strategy for treatment of brain tumors. One aspect of this approach is the bystander effect, which augments the efficacy of this therapeutic approach. Glioblastoma cells with minimum levels of connexin43 protein were transfected with a connexin43 complementary DNA. These cells manifested a marked increase in the in vitro bystander effect, supporting the contention that the in vitro bystander effect is a consequence of metabolic cooperation between cells mediated by gap junctions. To assess relative levels of gap-junction protein expression in the relevant tumor type, we examined primary astrocytomas, primary astrocytoma cell cultures, and glioblastoma cell lines. Although most astrocytoma tumor samples expressed connexin43, they differed in the level of expression, with the greatest variation exhibited in high-grade astrocytomas. Primary glioblastoma cell cultures and established glioblastoma cell lines also displayed some variability in connexin43 levels. In aggregate, our results anticipate that glioblastomas will have a varied bystander effect during HSV-tk gene therapy depending on the level of connexin43 expression.

Determination of the Lethal Dose of Dexamethasone for Early Passage In Vitro Human Glioblastoma Cell Cultures

Neurosurgery ◽  
1993 ◽  
Vol 33 (3) ◽  
pp. 485-488 ◽  
Author(s):  
Robert J. Maciunas ◽  
Robert A. Mericle ◽  
Christopher L. Sneed ◽  
Deborah J. Hefner ◽  
Patricia A. Commers ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Lethal Dose ◽  
Glioblastoma Cell ◽  
Early Passage ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell

Determination of the Lethal Dose of Dexamethasone for Early Passage In Vitro Human Glioblastoma Cell Cultures

Neurosurgery ◽  
1993 ◽  
Vol 33 (3) ◽  
pp. 485-488 ◽  
Author(s):  
Robert J. Maciunas ◽  
Robert A. Mericle ◽  
Christopher L. Sneed ◽  
Deborah J. Hefner ◽  
Patricia A. Commers ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Lethal Dose ◽  
Glioblastoma Cell ◽  
Early Passage ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell

In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours

1993 ◽  
Vol 29 (3) ◽  
pp. 416-420 ◽  
Author(s):  
Manfred Dietel ◽  
Ute Bals ◽  
Birgit Schaefer ◽  
Ingrid Herzig ◽  
Hartmut Arps ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Cultures ◽  
Primary Cell ◽  
Cytostatic Drug ◽  
Malignant Tumours ◽  
Primary Cell Cultures

Obtaining and Characterization of Alhagi persarum Boiss. et Buhse Callus Cell Cultures, Isoflavonoid Producers

2020 ◽  
Vol 36 (6) ◽  
pp. 35-48
Author(s):  
D.V. Коchkin ◽  
G.I. Sobolkovа ◽  
А.А. Fоmеnkov ◽  
R.А. Sidorov ◽  
А.М. Nоsоv
Keyword(s):  
Fatty Acids ◽  
Cell Culture ◽  
Liquid Chromatography ◽  
Secondary Metabolites ◽  
Cell Cultures ◽  
Mass Spectrometric ◽  
Mass Spectrometric Detection ◽  
Gas Liquid Chromatography ◽  
Callus Cell

The physiological characteristics of the callus cell cultures of Alhagi persarum Boiss et Buhse, a member of the legume family, widely used in folk medicine, have been studied. It was shown that the source of the explant was an important factor in the initiation of callusogenesis: more intense callusogenesis (almost 100%) was observed for explants from various organs of sterile seedlings, rather than intact plants (less than 30%). As a result, more than 20 lines of morphologically different callus cell cultures were obtained, and the growth parameters for the 5 most intensively growing lines were determined. The composition of fatty acids (FA) of total lipids and secondary metabolites in the most physiologically stable callus line Aр-207 was analyzed. Using capillary gas-liquid chromatography with mass spectrometric detection (GLC-MS), 19 individual C12--C24 FAs were identified, the main fraction of which were palmitic (~ 23%), stearic (~ 22%), linoleic (~ 14%) and α-linolenic (~ 33%) acids. The established atypical ratio of FAs (a simultaneous high content of both saturated FAs and polyunsaturated α-linolenic acid) is possibly due to the adaptation of cells to in vitro growth conditions. Phytochemical analysis of the secondary metabolites was carried out using ultra-performance liquid chromatography with electrospray ionization mass spectrometric detection (UPLC MS). Compounds belonging to different structural groups of isoflavones were found. Aglycones (calycosin, formononetin and afrormosin isomer), glucosides (formononetin glucoside), as well as esters of glucosides (malonylglycosides of calicosin, formononetin, afrormosin isomers, glycitein and genistein) were detected. These secondary metabolites are widespread in plants of the Fabaceae family; however, isoflavones are rare in representatives of the Alhagi genus. The presence of malonylated isoflavone glycosides in Alhagi spp. was shown for the first time. endemic plant species, Alhagi, in vitro cell culture, callus cell culture, isoflavones, fatty acids All studies were carried out using the equipment of the "Experimental Biotechnological Facility" and the "All-Russian Collection of Cell Cultures of Higher Plants" of IРР RAS. This work was supported by the Russian Foundation for Basic Research (RFBR), contract no.18-54-06021 (Az_a), and the Government of the Russian Federation, Megagrant Project no. 075-15-2019-1882.

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