5'-Nucleotidase activity and arachidonate metabolism in doxorubicin sensitive and resistant P388 cells

Ramu, A; Glaubiger, Daniel; Soprey, P; Reaman, Gregory H.; Feuerstein, Nili

doi:10.1038/bjc.1984.71

Cited by 27 publications

(25 citation statements)

References 15 publications

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“…Of interest were the pronounced levels of cholesteryl ester in all the cell lines. Others have reported only trace amounts in murine leukaemia cells (Ramu et al, 1984), and monkey and hamster kidney cells (Klenk and Choppin, 1969). However, we have found a large variation in cholesteryl ester levels for different cell types ranging from 2 nmol/lO* cells for mouse T cells up to 1653 nmol/lO* cells for the metastatic rat adenocarcinoma cell line, R13762 (Holmes et al,3 987).…”

Section: Discussionmentioning

confidence: 99%

Esterified cholesterol and triglyceride are present in plasma membranes of Chinese hamster ovary cells

Mackinnon

May

Mountford

1992

European Journal of Biochemistry

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The chemical composition of highly purified plasma membrane preparations from a series of malignant Chinese hamster ovary (CHO) cell lines were undertaken to ascertain if neutral lipid, including cholesteryl ester and triacylglycerol, were present. Triacylglycerols (33 -41 nmol/mg total lipid) and cholesteryl ester (226 -271 nmol/mg) were measured in the plasma membranes and differences in the chemical composition of these membranes recorded. The most significant difference was a gradual decrease in the level of free cholesterol from wild type (312 f 7 nmol/mg total plasma membrane lipid), Pod RII-6 (268 f 64 nmol/mg total plasma membrane lipid), Col R-22 (243 f 39 nmol/mg total plasma membrane lipid) to EOT (204 20 nmol/mg total plasma membrane lipid), with a concomitant increase in the degree of saturation of the cholesteryl ester fatty acids, particularly palmitic acid. No statistically significant differences were apparent in the chemical composition of the whole cells in this series.The one-dimensional (1D) 'H-NMR spectra of the four malignant cell lines showed a gradation in intensity of lipid resonances, in the order of wild type, Pod RII-6, Col R-22 and EOT, with EOT having the strongest lipid spectrum. Interestingly, the increase in acyl-chain signal intensities in the 'H-NMR spectra of this series of CHO cells and emergence of signals from cholesterol and/or cholesteryl ester, coincide with alterations in the amount of free choelsterol and the degree of saturation of the fatty-acyl chain of the esterified cholesterol in the plasma membranes.It is our hypothesis that, together, cholesteryl ester and triacylglycerol form domains in the plasma membrane and that when the cholesteryl ester has a largely saturated fatty acid content, the lipids are in isotropic liquid phase and hence visible by NMR.

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Section: Discussionmentioning

confidence: 99%

Esterified cholesterol and triglyceride are present in plasma membranes of Chinese hamster ovary cells

Mackinnon

May

Mountford

1992

European Journal of Biochemistry

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“…Considering that TAM can reverse MDRl-associated multidrug resistance [37], and that MCF-7/MDR cells are cross-resistant to TAM ( [38], and references therein), the observed stimulatory effects of TAM on PLD activity are of considerable interest. Among other possi- bilities, these data suggest that TAM might be able to modify multidrug resistance by stimulating its own efflux through mechanisms involving both the PLD system and P-glycoprotein.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen stimulates phospholipase D activity by an estrogen receptor‐independent mechanism

Kiss

1994

FEBS Letters

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The effects of tamoxifen (TAM), a widely used agent in the treatment of breast cancer, were examined on phospholipase D (PLD)-mediated phospholipid hydrolysis. In drug-sensitive MCF-7 human breast carcinoma cells TAM, similar to several well-established activators of PLD, had no effect on phospholipid hydrolysis. In an estrogen receptor-deficient multidrug-resistant subline of MCF-7 cells, TAM preferentially stimulated the hydrolysis of phosphatidylethanolamine; two-fold stimulation required 2.5 or 5/tM TAM in the absence or presence of serum, respectively. In NIH 3T3 fibroblasts significant (4-to 4.8-fold) stimulation of phosphatidylethanolamine and phosphatidylcholine hydrolysis in the presence of serum required 10/tM TAM. These data establish that TAM can stimulate PLD activity by an estrogen receptor-independent mechanism.

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“…brain [11] and melanoma [12], has sparked interest and elicited a move to understand the multimodal mechanisms of action of this synthetic triphenylethylene [3]. Among the most intriguing properties of tamoxifen, independent of estrogen receptor status, is reversal of multidrug resistance (MDR) [3,13,14]. This has resulted in clinical studies (1/ aimed at exploiting the chemosensitizing properties of tamoxifen [15,16].…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen retards glycosphingolipid metabolism in human cancer cells

et al. 1996

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In this study we provide evidence that tamoxifen, the widely used breast cancer drug, is a potent antagonist of glycolipid metabolism. When added to the medium of cultured multidrug resistant (MDR) KB-V-I carcinoma cells, tamoxifen, at 5.0 pM, drastically lowered the levels of glucosylceramide (glc-cer), as evidenced by a reduction in glc-cer mass. In a similar fashion, in cultured human melanoma cells grown with [3H]galactose, tamoxifen inhibited formation of glc-cer by 44%, and retarded lactosylceramide and ganglioside formation by 50 and 35%, respectively. When glc-cer synthase of melanoma was assayed in cell-free incubations, the inclusion of tamoxifen, at a I :I0 molar ratio with ceramide, inhibited glc-cer synthesis by 50%. These results clearly reveal a new action of tamoxifen and thereby pose intriguing questions regarding mechanisms of action in the realm of estrogen receptor-independent modalities, including effects on MDR.

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5'-Nucleotidase activity and arachidonate metabolism in doxorubicin sensitive and resistant P388 cells

Cited by 27 publications

References 15 publications

Esterified cholesterol and triglyceride are present in plasma membranes of Chinese hamster ovary cells

Esterified cholesterol and triglyceride are present in plasma membranes of Chinese hamster ovary cells

Tamoxifen stimulates phospholipase D activity by an estrogen receptor‐independent mechanism

Tamoxifen retards glycosphingolipid metabolism in human cancer cells

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