cytochalasin-b and Choriocarcinoma

The aim of this work was to investigate the putative modulation of glucose uptake in trophoblast cells by several dietary compounds and by drugs of abuse. For this, the acute (26 min) and chronic (48 h) effect of these substances on the apical uptake of 3H-2-deoxy-D-glucose (3H-DG) by a human choriocarcinoma cell line (BeWo) was determined. 3H-DG apical uptake by BeWo cells was time dependent, displayed saturable kinetics (Vmax=1210+/-29 nmol mg protein(-1) 6 min(-1) and Km=13.4+/-0.5 mM) and was insulin-insensitive and cytochalasin B-sensitive (by up to 60%). Acutely, acetaldehyde (30-100 mM), resveratrol, xanthohumol, epigallocatechin-3-gallate (100 microM), chrysin and quercetin (10-100 microM) decreased 3H-DG apical uptake, whereas rutin, catechin (10-100 microM), epicatechin (100 microM) and ethanol (10 mM) increased it. Quercetin and xanthohumol seem to be non-competitive inhibitors of 3H-DG apical uptake, whereas both epigallocatechin-3-gallate and acetaldehyde decreased both the Km and Vmax values. Chronically, rutin and myricetin increased the apical uptake of 3H-DG both isolated (0.1-1 microM) and in combination (both at 1 microM), whereas theophylline (0.1-1 microM) and amphetamine, 3,4-methylenedioxymethamphetamine (0.25-1 microM) and Delta9-tetrahydrocannabinol (1 nM) decreased it. In conclusion, 3H-DG apical uptake by BeWo cells is differentially modulated by different compounds present in drinks and by drugs of abuse.

Topics: Acetaldehyde; Amphetamine; Biological Transport; Caffeine; Cell Line, Tumor; Cell Survival; Choriocarcinoma; Cytochalasin B; Deoxyglucose; Diet; Dronabinol; Ethanol; Flavonoids; Glucose; Humans; Illicit Drugs; Kinetics; N-Methyl-3,4-methylenedioxyamphetamine; Nicotine; Phenols; Polyphenols; Theophylline; Trophoblasts

The role of extracellular matrix (ECM) in directing cell differentiation has been interpreted so far predominantly in terms of chemical signaling from individual matrix molecules. Recent data, however, suggest that the physical properties of ECM contribute signals for differentiation, which can be decisive and possibly even more important than chemical composition. In the present investigation, effects of different artificial matrices on the differentiation of BeWo choriocarcinoma cells were studied systematically. In Series (a) cells were grown on nonspecifically adhesive substrate gels (gels of glyoxyl agarose with or without poly-L-lysine crosslinked to) and on artificial matrix gels (matrix molecules covalently bound to agarose gels). Differentiation in terms of chorionic gonadotropin (hCG) secretion was stimulated on all artificial gel substrates much more than on rigid substrates of the same chemical composition. Concomitantly a change in morphology was observed to a rounded shape of cells in aggregates attached to the substrate. A series (b) of substrates with gradually reduced adhesiveness was created by coating plastic with different concentrations of poly-HEMA. In this sequence, gradual changes in cell morphology (stepwise approximation to a spherical shape) correlated with increased hCG secretion comparable to that on matrix gels. In contrast, in aggregates kept in suspension the increase in secretion of hCG was only marginal. These results clearly support that in addition to chemical recognition of individual matrix molecules, cells respond strongly to physical properties of extracellular matrix and that the physics of interaction of cytoskeleton, cell surface, and ECM can become decisive for cell differentiation.

Topics: Animals; Cell Differentiation; Cell Division; Cell Line; Choriocarcinoma; Chorionic Gonadotropin; Colchicine; Collagen; Cytochalasin B; Dimethyl Sulfoxide; Drug Combinations; Extracellular Matrix; Extracellular Matrix Proteins; Female; Gels; Glyoxylates; Humans; Laminin; Ligands; Pregnancy; Proteoglycans; Sepharose; Tumor Cells, Cultured; Uterine Neoplasms

Treatment of human choriocarcinoma cells with cytochalasin B at the doses of inhibiting cell division but not inhibiting nuclear division led to in vitro formation of the multinucleated syncytiotrophoblast-like ( STL ) cells. A concomitant increase in human chorionic gonadotropin (hCG) secretion per cell was noted. Immunocytochemical staining demonstrated the predominant localization of hCG in the STL cells. These results indicate that multinucleation stimulates hCG synthesis and secretion in the choriocarcinoma cells.

Topics: Cell Division; Cell Line; Cell Nucleus; Cells, Cultured; Choriocarcinoma; Chorionic Gonadotropin; Cytochalasin B; DNA; Female; Flow Cytometry; Humans; Pregnancy; Time Factors; Uterine Neoplasms