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Biomedical subjects

F Lauthier

Publications and source records attributed to F Lauthier.

4 recordsLinked to original sources

Flavonoids: structural requirements for antiproliferative activity on breast cancer cells.

Several classes of flavonoids (flavones, flavanones, 2'-hydroxychalcones and flavan-4-ols) having a variety of substituents on A ring were investigated for their antiproliferative activity against MCF-7 human breast cancer cells. Structure-activity relationships of these compounds were discussed. 2'-hydroxychalcones and methoxylated flavanones were found to be potent inhibitors of MCF-7 cells growth whereas flavones and flavan-4-ols appeared to be weak inhibitory agents except 7,8-dihydroxyflavone.

Antineoplastic Agents↗

Ursolic acid triggers calcium-dependent apoptosis in human Daudi cells.

Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs naturally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in human lymphoma Daudi cells in a dose-dependent manner. UA also induced morphological changes in cells as well as loss of membrane asymmetry, DNA fragmentation and nuclei condensation, indicating that the mechanism by which UA induced cell death was through apoptosis. Treatment with UA increased intracellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induced constituted the first steps of apoptosis.

Antineoplastic Agents, Phytogenic↗

Age-associated changes in mitochondrial parameters on peripheral human lymphocytes.

Among theories of aging, mitochondria are believed to be involved in senescence. Alterations of respiratory chain function and accumulation of various mitochondrial DNA mutations have been reported in mammalian postmitotic tissues. Because mitochondria have a central role in apoptosis and in adenosine triphosphate production, alteration of mitochondria function could contribute to immune senescence. We searched for alterations of mitochondrial parameters in peripheral lymphocytes with aging. Comparisons of respiratory chain activities of complex II+III, III, and IV were carried out in two populations of healthy volunteers with average ages of 35.3 +/- 6.7 years and 80.8 +/- 8.7 years. No difference was observed in complex IV activity between each group, whereas a significant decrease of complex II+III and a nonsignificant decrease of complex III activity were observed with aging. Alterations in mitochondrial functions can result from mutations in mitochondrial DNA (mtDNA), the most common being the 4977-bp deletion (mtDNA(-4977)). In either group we observed many deletions of mtDNA on peripheral blood lymphocytes by large-fragment polymerase chain reaction. This result suggests that alterations of respiratory chain activities observed with aging in lymphocytes could be the result of nuclear DNA dysfunction, with consequences on immune function (reduced responsiveness to antigen). Its possible implication on the recent observation of increased apoptosis of CD45RA+ RO- T cells with aging is discussed.

Adult↗

Mechanisms of zinc transport into pig small intestine brush-border membrane vesicles.

1. The purpose of the present work was to examine certain membrane transport mechanisms likely to carry zinc across the brush-border membrane of pig small intestine, isolated in a vesicular form. 2. In initial velocity conditions, saturation kinetics revealed a great effect of pH on zinc transport: optimal conditions were observed with an intravesicular pH of around 6.6 with or without a H+ gradient; however, this did not allow us to conclude the existence of a neutral exchange between Zn2+ and H+ ions. 3. By measuring 36Cl uptakes, the presence of the Cl(-)-HCO3- or Cl(-)-OH-antiporter with typical 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) sensitivity was detected in vesicles; zinc did not alter this anionic exchange activity. A 65Zn time course, performed in conditions identical with those for 36Cl uptake, was DIDS insensitive and was greatly inhibited by an outward OH- gradient. This could argue against a transport of zinc as a complex with Cl- and HCO3- through the anion antiporter. 4. When external Cl- and HCO3- were replaced by SCN-, able to form a Zn(SCN)4(2-) complex, we observed a stimulating effect of outward HCO3- gradients on 65Zn uptake but neither DIDS nor diphenylamine-2-carboxylate (DPC) inhibited the transport in these conditions. This suggested that the intestinal anion antiporter was not a major route for zinc reabsorption. 5. The tripeptide Gly-Gly-His at low concentrations stimulated 65Zn uptake, then inhibited it in a dose-dependent manner either in the presence of an inward H+ gradient or in the presence of a membrane potential 'negative inside' or in both situations. These conditions are necessary for the active transport of the peptide and this strongly suggests that zinc can be transported as a [Gly-Gly-His-Zn] complex, utilizing the peptide carrier system.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗