Similar effects of ether phospholipids, PAF and lyso-PAF on the Ca2+-ATPase activity of rat brain synaptosomes and leukocyte membranes

Grosman, Nina

doi:10.1016/s1567-5769(01)00064-9

Cited by 17 publications

(8 citation statements)

References 56 publications

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“…Edelfosine was found to act on membrane transporters and on ion channels that govern the influx and efflux of ions and nutrients. For example, edelfosine was found to inhibit Na + /H + exchanger (Besson, et al, 1996), Na + /K + ATPase (Zheng, et al, 1990) and to affect Ca 2+ -ATPase (Grosman, 2001).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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“…Ca 2+ -ATPase activity was assayed by measuring the release of inorganic phosphate from ATP as reported elsewhere [19]. The incubation mixture contained 40 mM Tris-HCl buffer (pH 7.0), 5 mM MgCl 2 , 50 mM KCl, 0.1 mM ouabain, 2 mM ATP (neutralized with hydroxide potassium (KOH)), microsomal protein (0.5-0.8 mg/ml) with either 2 mM EGTA or 20 mM CaCl 2 .…”

Section: Biochemical Analysismentioning

confidence: 99%

Chemical characterization of Lycium barbarum polysaccharides and their reducing myocardial injury in ischemia/reperfusion of rat heart

Zhao

2010

International Journal of Biological Macromolecules

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“…It is thought that this results in inhibitory effects upon mitogenic signal transduction pathways and disruption of the cell cycle. [8][9][10][11][12] Miltefosine was the first alkylphospholipid to be tested in the clinic. However, due to unacceptable toxicities with systemic administration, including hemolytic anemia with intravenous administration and gastrointestinal toxicities with oral administration, miltefosine use is currently limited to topical applications for the treatment of cutaneous metastases from breast cancer.…”

Section: Introductionmentioning

confidence: 99%

A phase II trial of perifosine, an oral alkylphospholipid, in recurrent or metastatic head and neck cancer

Argiris

Cohen

Karrison

et al. 2006

Cancer Biology & Therapy

109

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Background: Novel, effective therapies are warranted in the management of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Perifosine is an oral alkylphospholipid that inhibits AKT phosphorylation and has shown preclinical antitumor activity in head and neck cancer cell lines and xenografts.Patients And Methods: We conducted a phase II trial of perifosine in patients with incurable, recurrent or metastatic SCCHN. Previous therapy for recurrent or metastatic disease was limited to no more than one prior chemotherapy and one prior targeted/ biologic agent regimen. Patients had to have measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and adequate laboratory parameters. Perifosine was given as a loading dose of 150 mg every 6 hours × 6 doses orally in the first two days, with antiemetic prophylaxis, followed by 100 mg/day orally without interruption. Administration via gastrostomy tube was allowed. Tumor response was assessed every two cycles (eight weeks). Biomarkers in pathways potentially affected by perifosine, including AKT, P-AKT, P38, p53 and p21 were measured on tumor tissue by immunohistochemistry by manual and automated methods.Results: Nineteen patients were enrolled. No objective responses were observed. One patient had stable disease as best response and 18 patients progressed at first evaluation. The median overall survival time was 5.5 months and the median progression-free survival time was 1.7 months. The most frequent toxicities were gastrointestinal (constipation, nausea, vomiting) and fatigue. One patient developed grade 4 anorexia. Although the sample size was small, a significant correlation was detected between high expression of P38 and AKT in baseline tumor tissue and better survival.Conclusions: Perifosine in the doses and schedule used lacks single-agent activity in SCCHN. Our data do not justify further investigation of perifosine as a single agent in SCCHN.

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Similar effects of ether phospholipids, PAF and lyso-PAF on the Ca2+-ATPase activity of rat brain synaptosomes and leukocyte membranes

Cited by 17 publications

References 56 publications

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Chemical characterization of Lycium barbarum polysaccharides and their reducing myocardial injury in ischemia/reperfusion of rat heart

A phase II trial of perifosine, an oral alkylphospholipid, in recurrent or metastatic head and neck cancer

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