Can oxysterols work in anti-glioblastoma therapy? Model studies complemented with biological experiments

Wnętrzak, Anita; Kubisiak, Agata; Filiczkowska, Anna; Gonet-Surówka, Agnieszka; Chachaj‐Brekiesz, Anna; Targosz‐Korecka, Marta; Dynarowicz-Łątka, Patrycja

doi:10.1016/j.bbamem.2021.183773

Cited by 7 publications

(4 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, oxysterols can also be harmful to the body in case of their overproduction, which has been associated with many diseases and pathologies, for example those related to ageing processes such as: Alzheimer's disease (AD), age-related macular degeneration, cataracts, osteoporosis [8, 9,10], and also other neurodegenerative diseases, such as Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis [11,12,13,14] as well as cardiovascular disorders or several types of cancer [15,16,17,18]. However, the effect of oxysterols is not always negative -their multidirectional action is an intriguing issue.…”

Section: Introductionmentioning

confidence: 99%

Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model

Gonet-Surówka,

Ciechacka,

Kępczyński

et al. 2024

Cell Biochem Biophys

View full text Add to dashboard Cite

The study carried out systematic research on the in uence of selected oxysterols on cells viability, phospholipidosis and the level of secreted extracellular vesicles. Three oxidized cholesterol derivatives, namely 7α-hydroxycholesterol (7α-OH), 7-ketocholesterol (7-K) and 24-hydroxycholesterol (24-OH) were tested in three different concentrations: 50 μM, 100 μM and 200 μM for 24 hours incubation with A549 lung cancer cell line. All the studied oxysterols were found to alter cells viability. The lowest survival rate of the cells was observed after 24 h of 7-K treatment. Cells incubated with 24-OH had the best survival rate of all oxysterols used. 7-K increased phospholipids accumulation in cells but the strongest effect was observed for 24-OH. Changes in the level of extracellular vesicles secreted in cells culture were also observed. It was found that all oxysterols used increased the level of secreted vesicles, both exosomes and ectosomes. The strongest effect was noticed for 24-OH. Taken together, these results suggest that 7-K and 7α-OH are the most potent inducers of cancer cell death. The lower cytotoxic effect of 24-OH correlates with greater phospholipids accumulation, extracellular vesicles production and better cells survival.

show abstract

Section: Introductionmentioning

confidence: 99%

Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model

Gonet-Surówka,

Ciechacka,

Kępczyński

et al. 2024

Cell Biochem Biophys

View full text Add to dashboard Cite

show abstract

“…Meanwhile, an overproduction of oxidized sterols is associated with many diseases and pathologies . The multidirectional activity of oxysterols can lead to opposite effects; for example, they can act carcinogenic and antitumor. , It has also been shown that some sterols oxidized in the isooctyl chain (25-hydroxycholesterol (25-OH) and 27-hydroxycholesterol (27-OH)) can act against a wide spectrum of enveloped and nonenveloped viruses. , On the contrary, other oxysterols (independent of the additional polar group position in the sterol structure) were found to be significantly less effective in this respect or lacked antiviral activity.…”

Section: Introductionmentioning

confidence: 99%

Site of the Hydroxyl Group Determines the Surface Behavior of Bipolar Chain-Oxidized Cholesterol Derivatives─Langmuir Monolayer Studies Supplemented with Theoretical Calculations

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cholesterol oxidation products (called oxysterols) are involved in many biological processes, showing both negative (e.g., neurodegenerative) and positive (e.g., antiviral and antimicrobial) effects. The physiological activity of oxysterols is undoubtedly closely related to their structure (i.e., the type and location of the additional polar group in the cholesterol skeleton). In this paper, we focus on determining how a seemingly minor structural change (introduction of a hydroxyl moiety at C(24), C(25), or C(27) in the isooctyl chain of cholesterol) affects the organization of the resulting molecules at the phase boundary. In our research, we supplemented the classic Langmuir monolayer technique, based on the surface pressure and electric surface potential isotherms, with microscopic (BAM) and spectroscopic (PM-IRRAS) techniques, as well as theoretical calculations (DFT and MD). This allowed us to show that 24-OH behaves more like cholesterol and forms stable, rigid monolayers. On the other hand, 27-OH, similar to 25-OH, undergoes the phase transition from monolayer to bilayer structures. Theoretical calculations enabled us to conclude that the formation of bilayers from 27-OH or 25-OH is possible due to the hydrogen bonding between adjacent oxysterol molecules. This observation may help to understand the factors responsible for the unique biological activity (including antiviral and antimicrobial) of 27-OH and 25-OH compared to other oxysterols.

show abstract

“…It may seem counterintuitive that a more disordered plasma membrane results in a less deformable cell, but it has been suggested that disordered domains are the anchor points for actin molecules of the cytoskeleton underneath the lipid bilayer and thus the strengthened interaction of a disordered membrane to the underlying cytoskeleton can lead to increased cell stiffness [16][17][18]. Oxysterols have been found to increase endothelial cell stiffness [19,20] as well as the rigidity of single and multi-component Langmuir lipid monolayers [21,22]. Interestingly, 7-ketocholesterol was the oxysterol that caused the most pronounced effect [20,22].…”

Section: Introductionmentioning

confidence: 99%

“…Oxysterols have been found to increase endothelial cell stiffness [19,20] as well as the rigidity of single and multi-component Langmuir lipid monolayers [21,22]. Interestingly, 7-ketocholesterol was the oxysterol that caused the most pronounced effect [20,22]. A recent study of the effect of oxysterols on the stiffness of lipid monolayers mimicking the composition of the erythrocyte membrane and intact red blood cells showed that different oxysterols had opposing effects: whilst 7α-hydroxycholesterol decreased the stiffness, both 7-ketocholesterol and 7β-hydroxycholesterol increased membrane stiffness in these systems, with 7-ketocholesterol having again the strongest impact [23].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Cholesterol Oxidation on Erythrocyte Plasma Membranes: A Monolayer Study

et al. 2022

View full text Add to dashboard Cite

Cholesterol plays a key role in the molecular and mesoscopic organisation of lipid membranes and it is expected that changes in its molecular structure (e.g., through environmental factors such as oxidative stress) may affect adversely membrane properties and function. In this study, we present evidence that oxidation of cholesterol has significant effects on the mechanical properties, molecular and mesoscopic organisation and lipid–sterol interactions in condensed monolayers composed of the main species found in the inner leaflet of the erythrocyte membrane. Using a combination of experimental methods (static area compressibility, surface dilatational rheology, fluorescence microscopy, and surface sensitive X-ray techniques) and atomistic molecular dynamics simulations, we show that oxidation of cholesterol to 7-ketocholesterol leads to stiffening of the monolayer (under both static and dynamic conditions), significant changes in the monolayer microdomain organisation, disruption in the van der Waals, electrostatic and hydrophobic interactions between the sterol and the other lipid species, and the lipid membrane hydration. Surface sensitive X-ray techniques reveal that, whilst the molecular packing mode is not significantly affected by cholesterol oxidation in these condensed phases, there are subtle changes in membrane thickness and a significant decrease in the coherence length in monolayers containing 7-ketocholesterol.

show abstract

Can oxysterols work in anti-glioblastoma therapy? Model studies complemented with biological experiments

Cited by 7 publications

References 57 publications

Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model

Oxysterols in Cell Viability, Phospholipidosis and Extracellular Vesicles Production in a Lung Cancer Model

Site of the Hydroxyl Group Determines the Surface Behavior of Bipolar Chain-Oxidized Cholesterol Derivatives─Langmuir Monolayer Studies Supplemented with Theoretical Calculations

The Effects of Cholesterol Oxidation on Erythrocyte Plasma Membranes: A Monolayer Study

Contact Info

Product

Resources

About