Membrane-interactive lipids as experimental anticancer drugs

Berdel, W. E.

doi:10.1038/bjc.1991.277

Cited by 109 publications

(63 citation statements)

References 25 publications

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“…Ether lipids have been used in the therapy of cancer [3], since they are potent antineoplastic agents which inhibit growth, show antimetastatic activity and induce differentiation and apoptosis in cancer cells [4,5]. Immune stimulators properties have also been attributed to dietary ingestion of these substances [6].…”

Section: Introductionmentioning

confidence: 99%

A kinetic study of the lipase-catalyzed ethanolysis of two short-chain triradylglycerols: Alkylglycerols vs. triacylglycerols

Vázquez

Fernández

Blanco

et al. 2010

Journal of Molecular Catalysis B: Enzymatic

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Lipase-catalyzed ethanolysis of two short-chain triradylglycerols, namely tributyrin and 2,3-dibutyroil-1-O-alkylglycerols, have been studied. Much faster rate of reaction for the ethanolysis of tributyrin than that of 2,3-dibutyroil-1-O-alkylglycerols was attained. A kinetic model for the rate of release of ethyl butyrate and for the inactivation of the lipase has been also studied. The parameter corresponding to the release of ethyl butyrate was one order of magnitude higher for ethanolysis of tributyrin than the corresponding of 2,3-dibutyroil-1-O-alkylglycerols.On the contrary, the stability of Novozym 435 during ethanolysis of 2,3-dibutyroil-1-O-alkylglycerols was higher than the corresponding of tributyrin.At the reaction conditions under study, both ethanolysis reactions take place with high selectivity and yield monoesterified alkylglycerols and sn-2 monobutyrin as the main acylglycerols in the reaction mixtures.

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Section: Introductionmentioning

confidence: 99%

A kinetic study of the lipase-catalyzed ethanolysis of two short-chain triradylglycerols: Alkylglycerols vs. triacylglycerols

Vázquez

Fernández

Blanco

et al. 2010

Journal of Molecular Catalysis B: Enzymatic

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“…Several compounds, including ET18-OCH3, SRI 62-834, the thioether lipid BM 41.440 and hexadecylphosphocholine (HePC) (see Table I), are scheduled for, or currently undergoing, phase I/II clinical evaluation (Lohmeyer and Bittman, 1994). Considerable success has already been achieved with bone marrow purging (Berdel, 1991;Vogler, 1994). Topical application of HePC in breast cancer has also produced encouraging results (Dummer et al, 1992;Unger et al, 1992).…”

mentioning

confidence: 99%

“…Despite extensive laboratory and clinical studies, the major molecular mechanism of action of ATLs remains unclear (see Berdel, 1991;Lohmeyer and Bittman, 1994;Houlihan et al, 1995). Several plasma membrane proteins have been suggested as targets for ATLs, including the Na+/K+-ATPase membrane pump, Ca2+ channels, protein kinase C (PKC), phospholipase C (PLC) and PI-3-kinase (Shoji et al, 1988;Berdel, 1991;tJberall et al, 1991;Powis et al, 1992;Berggren et al, 1993).…”

mentioning

confidence: 99%

“…Synthetic anti-tumour lipids (ATLs), including the novel alkylphosphocholine derivatives, have emerged as effective agents in model systems and are currently undergoing clinical trials (Berdel et al, 1980;Berdel, 1991;Houlihan et al, 1995). Current preclinical and clinical experience with these agents has recently been comprehensively reviewed (Lohmeyer and Bittman, 1994).…”

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confidence: 99%

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Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Lohmeyer

Workman²

1995

Br J Cancer

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Summary A panel of 25 different lipid agents was evaluated for in vitro activity against HT29 human colon carcinoma and HL60 promyelocytic leukaemia cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships seen with this series, including those for four sets of positional or stereoisomers, indicate that specific receptor proteins are unlikely as targets for anti-tumour lipid (ATL) action. Additional data confirm the lack of involvement of the platelet-activating factor receptor in particular and suggest that metabolic stability is a most important determinant of ATL activity. More detailed studies, with 1-O-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ET18-OCH3) and (±)-2-{Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2-yl]methoxylphosphinyloxy)-N,N,N,-trimethylethaniminium hydroxide (SRI 62-834), suggest three different modes of activity, depending on drug concentration and exposure time. Low doses of up to 5 jiM in standard serum-containing medium cause population growth arrest after prolonged exposure. Growth arrest was associated with a leaky G2/M block as determined by flow cytometry. These effects are reversible. Intermediate concentrations (5-40 M) were cytotoxic, causing a net reduction in cell numbers after 2-3 days. At even higher concentrations, all lipids caused rapid, direct membrane lysis. When the clonogenic assay was used to assess the effects of ATLs, most agents reduced colony formation at concentrations above 5 jIM. However, some compounds proved stimulatory at nanomolar concentrations, suggesting that they might possess mitogenic properties. These results, particularly those concerning the concentration and time dependence, may be relevant to current clinical trials with ether lipids.

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“…One of these blockers is 1-O-octadecyl-2-O-methyl-lac-glycerol-3-phosphocholine which inhibits phosphatidylinositol phospholipase C with an IC,, of 0.4 pM. This compound is currently in phase Vphase I1 clinical trials (Berdel, 1993).…”

Section: Phospholipase Cmentioning

confidence: 99%

Signal‐Transduction Therapy

Levitzki

1994

European Journal of Biochemistry

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In the past decade it has become apparent that many diseases result from aberrations in signaling pathways. These include proliferative diseases such as cancers, atherosclerosis and psoriasis and inflammatory conditions such as sepsis, rheumatoid arthritis and tissue rejection. These findings refocused the research of the medical community to seek new modalities for disease management which essentially consist of designing drugs which intercept cell signaling. In this review, the emerging success in using tyrosine kinase blockers and other signal interceptors, such as protein kinase C blockers, Ras blockers, Ca2+ signaling inhibitors and estrogen antagonists which inhibit growth of cancer cells in vitro and in vivo, will be discussed. These signal interceptors, especially tyrosine‐kinase blockers, are also able to block inflammatory responses and the proliferation of vascular smooth muscle cells and psoriatic keratinocytes. The utility of signal interceptors in analyzing signal‐transduction pathways is also discussed.

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Membrane-interactive lipids as experimental anticancer drugs

Cited by 109 publications

References 25 publications

A kinetic study of the lipase-catalyzed ethanolysis of two short-chain triradylglycerols: Alkylglycerols vs. triacylglycerols

A kinetic study of the lipase-catalyzed ethanolysis of two short-chain triradylglycerols: Alkylglycerols vs. triacylglycerols

Growth arrest vs direct cytotoxicity and the importance of molecular structure for the in vitro anti-tumour activity of ether lipids

Signal‐Transduction Therapy

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