The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin

Rivel, Timothée; Ramseyer, Christophe; Yesylevskyy, Semen O.

doi:10.1038/s41598-019-41903-w

Cited by 119 publications

(125 citation statements)

References 109 publications

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“…The PM is highly organized and displays asymmetry with respect to the types of phospholipids found in inner and outer bilayer leaflets and with respect to FC distribution. For example, phosphatidylcholine (PC) predominates in the bilayer with a higher percentage of PC and SM in the outer leaflet while phosphatidylserine (PS) and phosphatidylethanolamine (PE) are preferentially found in the inner leaflet (9,10). Bilayers associated with intracellular organelles have somewhat different phospholipid to FC ratios and FC is reported to be asymmetrically distributed between the inner and outer leaflets (11)(12)(13).…”

Section: Microdomains and Cellular Cholesterol Homeostasismentioning

confidence: 99%

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Ouweneel

Thomas

Sorci‐Thomas

2020

Journal of Lipid Research

106

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Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.

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Section: Microdomains and Cellular Cholesterol Homeostasismentioning

confidence: 99%

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

Ouweneel

Thomas

Sorci‐Thomas

2020

Journal of Lipid Research

106

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“…Therefore, behind the individual molecular target of each chemotherapeutic agents, the potential effect on membrane bilayers, derived by the creation of amphiphilic molecules should be evaluated ( Bruno et al, 2013 ; Kumar et al, 2015 ). A better understanding of the biological effects of chemotherapeutic drugs on lipid membranes is essential to overcome MDR since, as mentioned before, cancer cells rearrange lipid composition and organization to avoid apoptosis and resist anticancer drugs ( Bernardes and Fialho, 2018 ; Rivel et al, 2019 ).…”

Section: Amphiphilic Molecules In Cancer Therapymentioning

confidence: 99%

New Insights Into Targeting Membrane Lipids for Cancer Therapy

Preta

2020

Front. Cell Dev. Biol.

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Modulation of membrane lipid composition and organization is currently developing as an effective therapeutic strategy against a wide range of diseases, including cancer. This field, known as membrane-lipid therapy, has risen from new discoveries on the complex organization of lipids and between lipids and proteins in the plasma membranes. Membrane microdomains present in the membrane of all eukaryotic cells, known as lipid rafts, have been recognized as an important concentrating platform for protein receptors involved in the regulation of intracellular signaling, apoptosis, redox balance and immune response. The difference in lipid composition between the cellular membranes of healthy cells and tumor cells allows for the development of novel therapies based on targeting membrane lipids in cancer cells to increase sensitivity to chemotherapeutic agents and consequently defeat multidrug resistance. In the current manuscript strategies based on influencing cholesterol/sphingolipids content will be presented together with innovative ones, more focused in changing biophysical properties of the membrane bilayer without affecting the composition of its constituents.

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“…The application of lipidbased drug carriers, that may affect the composition of membrane, its properties, and associated functions, is a strategy to sensitize cancer cells to anticancer agents. 47,48 Cholesterol is an important lipid molecule in animal cells as an essential constituent of the cell membrane and as a precursor for bile acids and steroid hormones. 49 The concentration of cholesterol within the plasma membrane, the cholesterol-to-phospholipid (C:PL) molar ratio, correlates with membrane microviscosity, and is influenced by cholesterol content in the surrounding environment.…”

Section: Suggested Mode Of Action: Cholesteryl Moiety Enables Two Waymentioning

confidence: 99%

<p>Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(<em>N</em>-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells</p>

Misiak¹,

Niemirowicz-Laskowska²,

Markiewicz³

et al. 2020

IJN

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Purpose: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cellpenetrating ligand, ie, cholesterol moiety, is a strategy to improve cellular uptake. Cholesterol end-capped poly(N-isopropylacrylamide)s offer a promising foundation for the design of efficient thermoresponsive drug delivery systems. Methods: A series of cholesterol end-capped poly(N-isopropylacrylamide)s (PNIPAAm) with number-average molar masses ranging from 3200 to 11000 g•mol-1 were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization from original xanthate-functionalized cholesterol and self-assembled into micelles. The physicochemical characteristics and cytotoxicity of cholesterol end-capped poly(N-isopropylacrylamide)s have been thoroughly investigated. Results: Phase transition temperature dependence on the molecular weight and hydrophilic/ hydrophobic ratio in the polymers were observed in water. Biological test results showed that the obtained materials, both in disordered and micellar form, are non-hemolytic, highly compatible with fibroblasts, and toxic to glioblastoma cells. It was found that the polymer termini dictates the mode of action of the system. Conclusion: The cholesteryl moiety acts as a cell-penetrating agent, which enables disruption of the plasma membrane and in effect leads to the restriction of the tumor growth. Cholesterol end-capped PNIPAAm showing in vitro anticancer efficacy can be developed not only as drug carriers but also as components of combined/synergistic therapy.

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The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin

Cited by 119 publications

References 109 publications

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes

New Insights Into Targeting Membrane Lipids for Cancer Therapy

<p>Evaluation of Cytotoxic Effect of Cholesterol End-Capped Poly(<em>N</em>-Isopropylacrylamide)s on Selected Normal and Neoplastic Cells</p>

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