New stable butyrate derivatives alter proliferation and differentiation in human mammary cells

Planchon, P.; Raux, Hélène; Magnien, V.; Ronco, G.; Villa, Pierre; Crépin, Michel; Brouty‐Boyé, Danièle

doi:10.1002/ijc.2910480323

Cited by 43 publications

(12 citation statements)

References 27 publications

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“…Butyrate also has potent effects on a variety of other cell types, including normal and malignant mammary epithelial cells [32, 33]. However, due to its rapid in vivo metabolism, it is difficult to achieve and maintain effective serum levels even when butyrate salts are administered by continuous i.v.…”

Section: Resultsmentioning

confidence: 99%

Stable Differences in Intrinsic Mitochondrial Membrane Potential of Tumor Cell Subpopulations Reflect Phenotypic Heterogeneity

Houston

Augenlicht

Heerdt

2011

International Journal of Cell Biology

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Heterogeneity among cells that constitute a solid tumor is important in determining disease progression. Our previous work established that, within a population of metastatic colonic tumor cells, there are minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (ΔΨm), and that these differences in ΔΨm are linked to tumorigenic phenotype. Here we expanded this work to investigate primary mammary, as well as colonic, tumor cell lines. We show that within a primary mammary tumor cell population, and in both primary and metastatic colonic tumor cell populations, there are subpopulations of cells with significant stable variations in intrinsic ΔΨm. In each of these 3 tumor cell populations, cells with relatively higher intrinsic ΔΨm exhibit phenotypic properties consistent with promotion of tumor cell survival and expansion. However, additional properties associated with invasive potential appear in cells with higher intrinsic ΔΨm only from the metastatic colonic tumor cell line. Thus, it is likely that differences in the intrinsic ΔΨm among cells that constitute primary mammary tumor populations, as well as primary and metastatic colonic tumor populations, are markers of an acquired tumor phenotype which, within the context of the tumor, influence the probability that particular cells will contribute to disease progression.

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Section: Resultsmentioning

confidence: 99%

Stable Differences in Intrinsic Mitochondrial Membrane Potential of Tumor Cell Subpopulations Reflect Phenotypic Heterogeneity

Houston

Augenlicht

Heerdt

2011

International Journal of Cell Biology

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“…It is generally considered to block cell cycle progression in G1 (25,30) but might also inhibit some cell types at a point in G2 (3). It is important to emphasize that a potential secondary inhibition in G2 would not affect the experimental strategy described above, where only the first blockage after Go would be apparent.…”

Section: Discussionmentioning

confidence: 99%

Cellular ras activity is required for passage through multiple points of the G0/G1 phase in BALB/c 3T3 cells.

Dobrowolski¹,

Harter²,

Stacey³

1994

Mol. Cell. Biol.

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Microinjection experiments demonstrated a requirement for cellular ras activity late in G1. In this study, we used two separate methods to identify an additional requirement for cellular ras activity early in the GO/GI phase of the cell cycle. Quiescent BALB/c cells were injected with anti-ras antibody prior to stimulation with serum. The cells would therefore be inhibited in progression through the cell cycle at the earliest point requiring ras function. Alternatively, cells were inhibited in late G1 as in previous studies by injecting anti (17). In support of this notion, a physical association between ras-GTP and cellular raf proteins has been demonstrated with several different experimental approaches (16,20,40,41,43,44).As further evidence that ras functions to transduce signals initiated by tyrosine kinases, the action of growth factor receptors leads to an elevation of the proportion of cellular ras associated with GTP (12, 31). Phosphorylated receptor molecules bind a number of proteins (22), including adapter molecules which associate with the ras exchange factor mSOS (2,4,8,11,23,29,33). It is likely that ras proteins are activated by the exchange factors positioned at the plasma membrane by their association with activated growth factor receptors. Genetic studies of Caenorhabditis elegans and Drosophila melanogaster have independently forged a link between ras, tyrosine kinases, and exchange factors. In each organism, the action of a developmentally required tyrosine kinase has been shown to * Corresponding author. Phone: (216) 444-0633. depend on a number of separate genes, including analogs for ras, ras exchange factors, and adapter proteins (7,13).While the data presented above leave little question that ras functions to transduce the signal initiated by growth factor receptors, there is a critical inconsistency between them in relationship to cell cycle timing. When quiescent cells are stimulated with serum and injected with anti-ras antibody (or either of the dominant ras inhibitors) at various times thereafter, DNA synthesis within the recipient cells is efficiently inhibited so long as the injection occurs prior to the initiation of S phase. This indicates that ras is required late in the G, phase of the cell cycle, presumably at the G1/S-phase boundary (21). The action of growth factors, however, alters ras activity much earlier in the cell cycle. The proportion of ras-GTP increases within 5 min following serum addition to quiescent cells (12,31). In addition, many of the intermolecular associations studies described above take place early in GJ/G1. Furthermore, injection of oncogenic ras into quiescent cells has been shown to induce the rapid expression of cellular fos protein, while the fos expression induced soon after growth factor addition can be partially inhibited by previous injection of anti-ras antibody (37). Finally, studies with dominant inhibitory ras mutants make it clear that the ability of peptide growth factors to stimulate mitogen-activated protein kinase activity is depende...

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“…The effect of the combined treatments on normal tissue morbidity is largely unknown, but there would be the advantage in the case of butyrate combined with radiotherapy that the effect of the combination would largely be restricted to the volume of the tumour. An alternative approach both for the butyrate alone or for combination with other therapy, is the use of derivatives of butyrate which are less readily metabolised (Planchon et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

The effect of sodium butyrate on the growth characteristics of human cervix tumour cells

Dyson¹,

Daniel²,

Surrey³

1992

Br J Cancer

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Summary Sodium butyrate has been shown to affect cell proliferation, and, at concentrations above approximately 0.5 mM, to cause cell death in some tumour cell lines. When combined with cytotoxic drugs increase in chemosensitivity has been observed. We are presently carrying out a study of the combined effects of sodium butyrate and cytotoxic drugs on cultured cervix tumour cells. To provide a baseline for this study we Prasad, 1980;Kruh, 1982;Nordenberg et al., 1987). Possibly combined with the effect of n-butyrate on cell proliferation is its action in reversibly inducing what has been termed a 'better differentiated phenotype', of increased radiosensitivity and chemosensitivity (Spremuli & Dexter, 1984). Due to these properties n-butyrate has been the subject of clinical investigations in leukaemic patients (Novogrodsky et al., 1983;Miller et al., 1987). Its effects when combined with cytotoxic drugs (Wasserman et al., 1989) or irradiation (Arundel & Leith, 1987; Leith et al., 1986) have also been investigated.We are presently carrying out an investigation of the effect of n-butyrate, when combined with a range of cytotoxic drugs, on cervix tumour cell lines when cultured as multicell spheroids. As a necessary preliminary to this study we have carried out a systematic investigation of the effect of nbutyrate alone on the growth characteristics of cervix tumour cells cultured as multicell spheroids. The effect of n-butyrate concentrations in the range 0.005 to 3 mM has been investigated, and the culture of the cells as multicell spheroids has allowed measurements over periods of up to 24 days. The results of this study are presented in this report. Materials and methods Cell cultureThe cervix tumour cell lines employed in this study were established in primary culture from cervix biopsy tissue taken routinely during radiotherapy at Cookridge Hospital (Dyson et al., 1984a). Six cell lines were used: 754, 612, 995, 090, 329, 708. These were maintained as monolayer cultures from which multicellular aggregates were obtained as required by using the method of Sutherland and Durand (1976). Spheroid cultures were initiated with the same number of spheroids per flask to allow intercomparison of cell counts during the period of the experiments. Multicell spheroids were maintained in culture as previously described (Boothby et al., 1989). Excess spheroids were discarded at the time of media change to maintain cell numbers approximately constant.The necessary volumes of 50 mM or 500 mM sodium nbutyrate solution were added to the spheroid suspensions at the start of the experiment to adjust to the concentrations shown in the figures, with further additions at media changes to maintain these concentrations. The butyrate solution was prepared from n-butyric acid (BDH Limited, Poole, UK) in Hanks basic salt solution, adjusted to pH 7.2 with NaOH solution, then sterilised by filtration through an 0.2 gtm Acrodisc (Gelman Sciences Limited, Northampton, UK).Spheroid diameter This was measured by means of a laser diffracti...

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New stable butyrate derivatives alter proliferation and differentiation in human mammary cells

Cited by 43 publications

References 27 publications

Stable Differences in Intrinsic Mitochondrial Membrane Potential of Tumor Cell Subpopulations Reflect Phenotypic Heterogeneity

Stable Differences in Intrinsic Mitochondrial Membrane Potential of Tumor Cell Subpopulations Reflect Phenotypic Heterogeneity

Cellular ras activity is required for passage through multiple points of the G0/G1 phase in BALB/c 3T3 cells.

The effect of sodium butyrate on the growth characteristics of human cervix tumour cells

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