Characteristics of the biphasic action of androgens and of the potent antiproliferative effects of the new pure antiestrogen EM-139 on cell cycle kinetic parameters in LNCaP human prostatic cancer cells

The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nM DHT, analysis of cell kinetic parameters shows a decrease of the G0-G1 fraction with a corresponding increase of the S and G2 + M fractions. In contrast, concentrations of 1 nM DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G0-G1 fraction at the expense of the S and especially the G2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5'-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.

Stimulation of apolipoprotein D secretion by steroids coincides with inhibition of cell proliferation in human LNCaP prostate cancer cells

Although steroid hormones are known to play a predominant role in the regulation of cell growth in hormone-sensitive cancers, their mechanisms of action, especially their interaction with growth factors and/or growth inhibitors, is poorly understood. We have recently observed that the effects of androgens and estrogens on the expression of the major protein found in human breast gross cystic disease fluid, protein-24, are opposite to their respective action on cell proliferation in human breast cancer cell lines. Somewhat surprisingly, the recent elucidation of the amino acid sequence of this progesterone binding protein reveals that this tumor marker is apolipoprotein D (apo D), a member of a superfamily of lipophilic ligand carrier proteins. The present study was designed to determine whether apo D is secreted by human prostate cancer cells and could thus be a new marker of steroid action in these cancer cells, and whether the sex steroid-induced stimulation of apo D secretion coincides with inhibition of cell proliferation. We took advantage of the biphasic pattern of the effect of steroids on the proliferation of the human prostate cancer LNCaP cell line, which offers the opportunity to discriminate between positive and negative steroid receptor-regulated cell growth processes. A 10-day exposure to low concentrations of dihydrotestosterone and testosterone caused a potent stimulation of LNCaP cell proliferation, whereas incubation with higher concentrations of these androgens led to a progressive decrease in cell proliferation towards basal levels. The biphasic action of androgens was also observed on apo D secretion, the effects on apo D secretion being inversely related to their action on LNCaP cell proliferation. Similar opposite biphasic effects were also observed with 9 other steroids, thus indicating that the stimulation of secretion of this new biochemical marker coincides with inhibition of cell proliferation in LNCaP human prostatic cancer cells.

Effects Of Aromatic-Hydrocarbons On The Metabolism Of The Digestive Gland Of The Mussel Mytilus-Edulis-L

1. The results presented in this paper show that the exposure of mussels to a sublethal concentration of oil-derived aromatic hydrocarbons (30 μg 1−1) for a period of 4 months significantly decreases the protein level in the digestive gland of the animals (−17%). 2. The activity of the nuclear RNA polymerase I and II is also significantly decreased in the digestive gland of hydrocarbon-exposed mussels (−64% and −18%, respectively). 3. The RNAase(s) activity present in the nuclei from the digestive gland cells increases following the exposure of the mussels to aromatic hydrocarbons. This effect is particularly evident at high ionic strength [200 mM (NH4)2SO4]. 4. The analysis of some characteristics of the nuclear RNAase(s) (most of which is soluble and shows a maximum of activity at pH 4−5) could indicate that part of this hydrolytic enzyme may have a lysosomal origin. 5. This fact appears to be in agreement with the finding that in the mussels exposed for 4 months to aromatic hydrocarbons the lysosomal stability decreases drastically and the total content of lysosomal enzymes is significantly increased (+42.4%).

Aerobic Metabolism Octopine Production And Phosphoarginine As Sources Of Energy In The Phasic And Catch Adductor Muscles Of The Giant Scallop Placopecten-Magellanicus During Swimming And The Subsequent Recovery Period

1. The energy contributions of aerobic metabolism, phosphoarginine, ATP and octopine in the adductor muscles of P. magellanicus were examined during swimming and recovery. 2. A linear relationship was observed between the size of the phosphoarginine pool and the number of valve snaps. A linear increase in arginine occurred during the same period. 3. 3. Octopine was formed during the first few hours of recovery, particularly in the phasic muscle. 4. The restoration of the phosphoarginine pool appeared to be by aerobic metabolism. 5. It is concluded that the role of octopine formation is to supply energy when the tissues are anoxic and to operate at such a rate as to maintain the basal rate of energy production.