Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

Henke, Guido; Meier, Verena; Lindner, Lars H.; Eibl, H.; Bamberg, M.; Belka, Claus; Budach, Wilfried; Jendrossek, Verena

doi:10.1186/1748-717x-7-172

Cited by 10 publications

(7 citation statements)

References 38 publications

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“…Both in vitro and in vivo assays have shown promising antitumor activity of erufosine alone and in combination with radiation on astrocytoma and glioblastoma cell lines (Awde, et al, 2013;Rubel, et al, 2006). However, a preclinical in vivo study analyzing the effect of ionizing radiation in combination with erufosine on T98G glioblastoma xenograft tumors showed a transient decrease in the growth of the T98G tumors, but failed to improve efficacy of fractionated irradiation in terms of local tumor control (Henke, et al, 2012).…”

Section: Accepted Manuscriptmentioning

confidence: 94%

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: 94%

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

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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“…The other inhibitors of AKT phosphorylation, AktX (Fig. 2 d) and erufosine, also caused a significant growth inhibition of GBM cell lines or GBM xenograft tumors, respectively [ 51 , 52 ]. Inhibition of AKT’s kinase activity by AktX resulted in a reduction of GSK3β phosphorylation which in turn activated GSK3β [ 51 ].…”

Section: Akt and Gsk3β As Therapeutic Targets In Gbmmentioning

confidence: 99%

AKT/GSK3β Signaling in Glioblastoma

2016

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Glioblastoma (GBM) is the most aggressive of primary brain tumors. Despite the progress in understanding the biology of the pathogenesis of glioma made during the past decade, the clinical outcome of patients with GBM remains still poor. Deregulation of many signaling pathways involved in growth, survival, migration and resistance to treatment has been implicated in pathogenesis of GBM. One of these pathways is phosphatidylinositol-3 kinases (PI3K)/protein kinase B (AKT)/rapamycin-sensitive mTOR-complex (mTOR) pathway, intensively studied and widely described so far. Much less attention has been paid to the role of glycogen synthase kinase 3 β (GSK3β), a target of AKT. In this review we focus on the function of AKT/GSK3β signaling in GBM.

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“…Complete and sustained regression of squamous cell carcinoma xenografts occurred after combined treatment of radiation and perifosine (Vink et al, 2006). Short-term treatment with erufosine produced only a transient decrease in the growth of the T98G glioblastoma tumors that was enhanced by repeated application (Henke et al, 2012). These data suggest that in vivo efficacy may depend on an extended treatment schedule.…”

Section: Development Of Drug Combinations Containing Alpsmentioning

confidence: 90%

Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs

Murray

Hraiki

Bebawy

et al. 2015

Pharmacology & Therapeutics

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Lipids have the potential for development as anticancer agents. Endogenous membrane lipids, such as ceramides and certain saturated fatty acids, have been found to modulate the viability of tumor cells. In addition, many tumors over-express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the biotransformation of ω-6 polyunsaturated fatty acids (PUFAs) to potent eicosanoid regulators of tumor cell proliferation and cell death. In contrast, several analogous products from the biotransformation of ω-3 PUFAs impair particular tumorigenic pathways. For example, the ω-3 17,18-epoxide of eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling cascades in tumor cells and the lipoxygenase-derived resolvins are effective inhibitors of inflammatory pathways that may drive tumor expansion. However, the development of potential anti-cancer drugs based on these molecules is complex, with in vivo stability a major issue. Nevertheless, recent successes with the antitumor alkyl phospholipids, which are synthetic analogues of naturally-occurring membrane phospholipid esters, have provided the impetus for development of further molecules. The alkyl phospholipids have been tested against a range of cancers and show considerable activity against skin cancers and certain leukemias. Very recently, it has been shown that combination strategies, in which alkyl phospholipids are used in conjunction with established anticancer agents, are promising new therapeutic approaches. In future, the evaluation of new lipid-based molecules in single-agent and combination treatments may also be assessed. This could provide a range of important treatment options in the management of advanced and metastatic cancer.

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Effects of ionizing radiation in combination with Erufosine on T98G glioblastoma xenograft tumours: a study in NMRI nu/nu mice

Cited by 10 publications

References 38 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

AKT/GSK3β Signaling in Glioblastoma

Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs

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