Interaction of a quercetin derivative - lensoside Aβ with liposomal membranes

Pawlikowska-Pawlęga, Bożena; Kapral, J.; Gawron, Antoni; Stochmal, Anna; Żuchowski, Jerzy; Pecio, Łukasz; Luchowski, Rafał; Grudziński, Wojciech; Gruszecki, Wiesław I.

doi:10.1016/j.bbamem.2017.10.027

Cited by 11 publications

(8 citation statements)

References 44 publications

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“…In summary, we have demonstrated for the first time that lensoside Aβ intensifies the anticancer potential of sorafenib, synergistically enhancing the susceptibility of human glioblastoma multiforme and anaplastic astrocytoma cells to apoptosis initiation. This could be correlated with the previously confirmed ability of the flavonoid to interact with membrane structures [ 18 ], which, as a consequence, could lead to morphological changes typical for programmed death. It also seems that the Ras–Raf–MEK–ERK pathway may play a key role in this process.…”

Section: Discussionsupporting

confidence: 78%

“…The FLIM technique revealed the presence of extramembranous vesicles attached to the cells upon the separate lensoside Aβ treatment and in combination with sorafenib. Such morphological changes may be a response to the flavonoid gradually penetrating into the cells, as LAβ is known for its intercalation and interaction with membranes, changing their structure and properties as a consequence [ 18 ]. Interestingly, this effect was accelerated by the additional sorafenib incubation.…”

Section: Discussionmentioning

confidence: 99%

“…One of them is lensoside Aβ (LAβ), representing quercetin glycoside. As presented in the first (and the only so far) article, it is able to intercalate into the cell membrane and interact with its structures, which in consequence may have beneficial effects [ 18 ]. Our previous experiments revealed that quercetin has anticancer properties, with special emphasis on glioma cells [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Lensoside Aβ as an Adjuvant to the Anti-Glioma Potential of Sorafenib

Maciejczyk

Kapral-Piotrowska

Sumorek-Wiadro

et al. 2021

Cancers

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Aim: The anti-glioma effect of lensoside Aβ alone and in combination with sorafenib (pro-survival Raf kinase inhibitor) was evaluated for the first time in terms of programmed cell death induction in anaplastic astrocytoma and glioblastoma multiforme cell lines as an experimental model. Apoptosis, autophagy, and necrosis were identified microscopically (fluorescence and scanning microscopes) and confirmed by flow cytometry (mitochondrial membrane potential MMP and cell death). The expression of apoptotic (caspase 3) and autophagic markers (beclin 1) as well as Raf kinase were estimated by immunoblotting. The FTIR method was used to determine the interaction of the studied drugs with lipid and protein groups within cells, while the modes of drug action within the cells were assessed with the FLIM technique. Results: Lensoside Aβ itself does not exhibit anti-glioma activity but significantly enhances the anti-cancer potential of sorafenib, initiating mainly apoptosis of up to 90% of cells. It was correlated with an increased level of active caspase 3, a reduced MMP value, and a lower level of Raf kinase. The interaction with membrane structures led to morphological changes typical of programmed death. Conclusions: Our results indicate that lensoside Aβ plays an important role as an adjuvant in chemotherapy with sorafenib and may be a potential candidate in anti-glioma combination therapy.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lensoside Aβ as an Adjuvant to the Anti-Glioma Potential of Sorafenib

Maciejczyk

Kapral-Piotrowska

Sumorek-Wiadro

et al. 2021

Cancers

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“…Quercetin [132,173,282,[342][343][344][345][346][347][348], Biochanin [183], Argenteane [132,171], α-Tocopherol [173,[349][350][351][352], Ascorbic acid [173], Carbazoles [172], Anthocyanin derivatives (Hemiketal, Chalcone, Pyranoanthocyanin, Aglycone, A4, A5, A7, A-4 7) [353], Trolox [354],…”

Section: Antioxidantsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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“…Because of stochasticity, the lag phase is highly susceptible to heterotypic interactions with other solutes present in the system. From years of research, we have known that the Aβ ‘interactome’ includes a variety of agents such as metal ions [29, 30], protein binding partners [31, 32], natural products and metabolites [33–37], as well as lipids and surfactants (as elaborated in this article). Therefore, heterotypic interactions with any Aβ interactome molecules have the potential to change the conformation of Aβ during the lag phase and alter the pathway of aggregation, which could result in multiple conformational variants of aggregates with distinct biochemical and cellular properties.…”

Section: Aggregation Of Aβ and Significance Of Pathwaysmentioning

confidence: 99%

Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis

Rangachari

Dean

Rana

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction. The aggregation process is highly stochastic involving both homotypic (Aβ-Aβ) and heterotypic (Aβ with interacting partners) interactions. Two of the important members of interacting partners are membrane lipids and surfactants, to which Aβ shows a perpetual association. Aβ-membrane interactions have been widely investigated for more than two decades, and this research has provided a wealth of information. Although this has greatly enriched our understanding, the objective of this review is to consolidate the information from the literature that collectively showcases the unique phenomenon of lipid-mediated Aβ oligomer generation, which has largely remained inconspicuous. This is especially important because Aβ aggregate "strains" are increasingly becoming relevant in light of the correlations between the structure of aggregates and AD phenotypes. Here, we will focus on aspects of Aβ-lipid interactions specifically from the context of how lipid modulation generates a wide variety of biophysically and biochemically distinct oligomer sub-types. This, we believe, will refocus our thinking on the influence of lipids and open new approaches in delineating the mechanisms of AD pathogenesis. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.

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Interaction of a quercetin derivative - lensoside Aβ with liposomal membranes

Cited by 11 publications

References 44 publications

Lensoside Aβ as an Adjuvant to the Anti-Glioma Potential of Sorafenib

Lensoside Aβ as an Adjuvant to the Anti-Glioma Potential of Sorafenib

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Cause and consequence of Aβ – Lipid interactions in Alzheimer disease pathogenesis

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