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M Motta

Publications and source records attributed to M Motta.

At least 19 recordsLinked to original sources
PubMed2001

Aromatase expression and activity in male and female cultured rat hypothalamic neurons: effect of androgens.

Aromatase is possibly involved in male brain sexual differentiation. Aim of these experiments was to evaluate the role of testosterone (T) and of DHT, in the regulation of aromatase expression and activity. The experiments were done utilizing rat primary cultures of hypothalamic neurons from 16-day old embryos sex-screened by SRY gene. Aromatase expression was assessed semiquantitatively by RT-PCR using a neuronal marker (MAP2c) as coamplification product; enzymatic activity was estimated by the 3H(2)O method. The results indicate that (1) cultured neurons possess a functional aromatase, which increases significantly during a 5-days culture period; (2) neurons from males possess a higher expression and activity of the enzyme than females; (3) androgens negatively control expression/activity of aromatase in males, DHT is more active than T; (4) on the contrary, in females T produces a small stimulation of aromatase expression, but not of activity (DHT has produced inconsistent results). The results obtained in this model indicate that T does not stimulate aromatase; therefore, it is not responsible for triggering the perinatal enzymatic peak, nor for the sexual dimorphic aromatase expression. A model is proposed in which DHT might induce, at least in males, the descending phase of the aromatase peak.

Animals↗
PubMed2001

Oncostatic activity of a thiazolidinedione derivative on human androgen-dependent prostate cancer cells.

Thiazolidinedione derivatives with potent antiarthritic activity, such as CGP 52608, have been suggested to exert their biological effects through the activation of the orphan nuclear receptor RORalpha. Since response elements for this receptor are present in the promoter region of cell cycle-related genes (i.e., p21(WAF1/CIP1) and cyclin A), we reasoned that CGP 52608 might affect cell proliferation, cell cycle progression and the expression of cell cycle-related genes. This hypothesis has been verified in the human androgen-dependent prostate cancer cell line LNCaP. We found that the treatment of LNCaP cells with CGP 52608 brings about a significant and dose-dependent decrease of cell proliferation. Thiazolidinedione affected cell cycle distribution, inducing an accumulation of the cells in the G0/G1 phase and a decrease in the S phase. This effect was accompanied by an increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and a decreased expression of cyclin A. These data indicate that, in human androgen-dependent LNCaP prostate cancer cells, the thiazolidinedione derivative CGP 52608 exerts a strong cytostatic activity, by reducing cell proliferation and by affecting cell cycle distribution through the modulation of the expression of cell cycle-related genes. These biological actions of CGP 52608 might be mediated by the activation of the orphan nuclear RORalpha receptor, which is expressed in LNCaP cells.

Androgens↗
PubMed2001

Somatostatin up-regulates topoisomerase II alpha expression and affects LNCaP cell cycle.

mRNA differential display-PCR analysis was used to perform a systematic screening of Somatostatin (SS)-regulated genes in the human prostatic carcinoma cell line LNCaP (Lymph Node Carcinoma of the Prostate). A 170 bp fragment was shown to be up-regulated by SS. Sequence analysis of this fragment revealed its homology with the human Topoisomerase II Alpha gene. Up-regulation of Topoisomerase II Alpha was confirmed by Northern blot hybridisation and was induced by the same dose of SS (1 nM) earlier demonstrated to inhibit LNCaP cell growth. Furthermore, SS possible effects on timing, as well as concentration of Topoisomerase II Alpha along the different phases of the cell cycle were investigated. To this purpose changes in the enzyme protein concentration in response to SS were assessed in synchronised LNCaP cells. The hormone was shown to exert a perturbing effect on both parameters considered, possibly related to its inhibitory action on LNCaP cell replication.

Antigens, Neoplasm↗
PubMed2001

Activation of the orphan nuclear receptor RORalpha induces growth arrest in androgen-independent DU 145 prostate cancer cells.

BACKGROUND: RORalpha is a transcription factor which belongs to the family of orphan nuclear receptors. The regulatory functions of this receptor are still poorly understood. However, response elements for RORalpha are present on the promoter of cell cycle-related genes suggesting that it might be involved in the control of cell proliferation. In this study, we investigated the expression and the possible function of RORalpha in a human androgen-independent prostate cancer cell line (DU 145). The thiazolidinedione-derivative CGP 52608 has been utilized as the specific ligand and activator of RORalpha. METHODS: The effects of CGP 52608 on DU 145 cell proliferation and cell cycle distribution were analyzed by hemocytometer and by FACS analysis, respectively. The expression of RORalpha as well as the effects of RORalpha activation on the expression of cell cycle-related genes were evaluated by RT-PCR. To clarify whether RORalpha activation might affect the proliferation of prostate cancer cells also in vivo, nude mice bearing DU 145 tumor xenografts were treated with CGP 52608 at different doses and the growth of the tumors was followed by caliper measurement. RESULTS: RORalpha is expressed in DU 145 cells and the treatment of the cells with the thiazolidinedione-derivative CGP 52608 brought about a dose-dependent and significant decrease of cell proliferation. Ligand-induced activation of RORalpha affected cell cycle distribution, inducing an accumulation in the G(0)/G(1) phase and a decrease in the S phase. This effect was accompanied by an increased expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and a decreased expression of cyclin A. The growth of DU 145 tumors in nude mice was significantly reduced by treatment with CGP 52608. CONCLUSIONS: These data indicate that, in androgen-independent DU 145 prostate cancer cells, activation of the orphan nuclear receptor RORalpha inhibits cell growth, both in vitro and in vivo. RORalpha also induces cell cycle arrest, possibly through the modulation of the expression of cell cycle-related genes.

Animals↗
PubMed2001

Effectiveness of geriatric evaluation and care. One-year results of a multicenter randomized clinical trial.

The aim of this study was to demonstrate the effectiveness of outpatient elderly care based on Comprehensive Geriatric Assessment (CGA). Eleven hospital Geriatric Evaluation and Management units (GEMs) systematically screened 1386 inpatients over a 10-month period, using the same uniform selection plan which included 15 programmed exclusion-inclusion criteria and a standard CGA. At the end of this screening, 152 eligible frail elderly patients were randomized to either a comprehensive outpatient GEMs program (intervention group: N=79) or to usual care by their family doctors (control group: N=73). We did not find any statistically significant difference between the two groups at entry. During the one-year follow-up period, 6 GEMs patients (7.6%) and 12 controls (17.1%) died, without significant differences between the two survival curves. Only three patients (all controls) ultimately dropped out, and eight (3 unit patients and 5 controls) entered a nursing home. GEMs patients were significantly more likely to have individual improvement in mental status (p=0.006), morale (p=0.024) and functional level (p=0.023), compared to controls. Even though intervention participants spent fewer days in hospital and nursing home (p<0.05), they received much more home care and day-hospital assistance (p<0.001), which explains why total expenditure on health care was the same in the two groups. We conclude that: 1) a standardized selection plan may contribute to identify the older inpatients in need of CGA; and 2) CGA-based outpatient care may be clinical- and cost-effective if directly managed by GEMs, and may provide targeted older patients with more substantial benefits than standard care, without inflating health care expenses.

Aged↗
PubMed2001

Control of the expression of human neuropeptide Y by leptin: in vitro studies.

Neuropeptide Y (NPY) participates in the regulation of reproduction and food intake. The adipose-secreted hormone, leptin, has also been involved in these processes, and has been shown to exert its effects in part by controlling NPY synthesis and release at the hypothalamic level. In the present study, we utilized the SH-SY5Y human neuroblastoma cell line, to study the leptin-NPY interrelationships. SH-SY5Y cells were found to express leptin receptors (RT-PCR and Western blot analyses). A 24-h treatment with leptin at different concentrations did not affect NPY gene expression, but resulted in a stimulation of NPY release. This stimulated secretion was blocked by the combined treatment with leptin and the muscarinic agonist carbachol or the phorbol ester TPA. Leptin and carbachol also caused an increased intracellular content of NPY. In conclusion, the SH-SY5Y human neuroblastoma cell line appears to be a suitable in vitro model for studying the pharmacological effects of leptin on the biosynthesis and secretion of NPY.

Blotting, Northern↗
PubMed2001

Proton magnetic relaxation in bone marrow related to age and bone mineral density: low-resolution in vitro studies.

Detailed analysis of proton spin-spin and spin-lattice relaxation behaviors of the bone marrow in the presence of trabecular bone network was performed at low-resolution (B(0) = 0.496T) on rat vertebrae specimens deprived of spinal cord. Two groups of samples, from young and old healthy animals, were investigated before cellular necrosis had started. BMD measurements were carried out to quantify the expected age-related modifications of the trabecular bone network. 1H-MR measurements were also performed on the same samples, deprived of marrow and saturated with water, in order to control the validity of a possible interpretation of the marrow 1H-MR characteristics, in terms of marrow components, and to investigate the possible employment of these samples to study the trabecular bone network properties. We pointed out that: 1) a bimodal distribution of T(2i) and T(1i) values (distinguishing "fast" and "slow" relaxations) describes satisfactorily all the 1H-MR experimental decays; 2) age-related modifications of the trabecular bone network are marked by correlate variations of the BMD value and of the proton spin-spin relaxation rates in water saturated samples; 3) age-related modifications of marrow are underlined by variations of the average value of the "fast" T(2i) and of the "slow" T(1i) relaxation time distributions, which could be attributed to the marrow components different from the fat granules of the adipose cells. Our results suggest that studies in vitro on bone tissue, by 1H-MR techniques at low-resolution, may contribute to a better bone function characterization and, therefore, to a better clinical utilization of MRI techniques.

Aging↗
PubMed2001

Biological and molecular characterization of PNH-like lymphocytes emerging after Campath-1H therapy.

Campath-1H, an anti-CD52 monoclonal antibody, is therapeutically active in lymphoproliferative and autoimmune diseases. After Campath-1H therapy, lymphocytes with a paroxysmal nocturnal haemoglobinuria (PNH) phenotype have been reported to emerge. We characterized a PNH-like lymphocyte population emerging after Campath-1H therapy, in a patient with fludarabine refractory B-cell chronic lymphocytic leukaemia (B-CLL). We demonstrated a reduction in PIG-A mRNA levels compared with controls, and of all cytokines tested [interleukin (IL)-4, IL-13, IL-2, interferon(IFN)-gamma, IL-6, IL-10, and tumour necrosis factor (TNF)-alpha], except transforming growth factor (TGF)-beta. Given the inhibitory activity of TGF-beta, its elevated levels may contribute to the selective pressure of Campath-1H, leading to the emergence of PNH-like lymphocytes.

Alemtuzumab↗
PubMed2001

Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy.

Hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, may develop in 20-50% of hepatitis B virus surface antigen (HbsAg)-positive patients undergoing immunosuppressive or cytostatic treatment. Lamivudine is a nucleoside analogue that can directly suppress HBV replication. We have performed a pilot study to test the efficacy and tolerability of lamivudine as a primary prophylaxis of HBV reactivation in 20 consecutive patients treated for haematological malignancies, mainly of lymphoid origin. Lamivudine, 100 mg/d, was given orally from the start until 1 month after the end of chemotherapy, which included corticosteroids and/or purine analogues in 85% of cases. It was well tolerated and did not cause any unexpected reduction of cytostatic drugs dosages. The chemotherapy programme was completed in all patients without modifications. A transient threefold increase in serum amylase was observed in one case. HBV-DNA levels decreased in six out of six patients (P = 0.039) and ALT levels in five out of six patients (P = 0.057) whose serum levels were abnormal at the onset of therapy. Two patients developed transient hepatitis. HBV reactivation was documented in only one of these patients who had stopped lamivudine 1 month before. No signs of HBV reactivation were detected both during and after treatment in 18 patients with a median follow-up of 6 months (range 3-12). Thus, primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HBsAg carriers.

Adult↗
PubMed2001

Expression of neuropeptide Y receptors in human prostate cancer cells.

BACKGROUND: Neuroendocrine molecules are now believed to play a significant role in the progression of human prostate cancer (CaP), especially in the androgen-independent stage. MATERIALS AND METHODS: In the present study, we evaluated the presence and the function of the receptors for neuropeptide Y (NPY) in human CaP cell lines (the androgen-dependent LNCaP, and the androgen-independent DU 145 and PC-3). RESULTS: The presence of high-affinity binding sites for NPY was shown on PC-3 cells (radioreceptor assay). Reverse transcription-polymerase chain reaction analysis indicated that these sites correspond to the Y1 and Y2 receptor isoforms. A Y1 receptor protein (70 kDa) was also detected in PC-3 cell extracts by Western blot analysis. The activation of these receptors by NPY resulted in a reduction of forskolin-induced cAMP accumulation and an increase of [Ca2+]i. Moreover, a prolonged treatment with NPY induced a dose-related proliferation of PC-3 cells. CONCLUSIONS: By showing that NPY receptors are expressed in the androgen-independent cell line PC-3 and that their activation results in cell proliferation, the present date suggest that NPY-related mechanisms might be relevant in certain stages of CaP, such as the progression of the disease during the androgen-independent stage.

Androgens↗
PubMed2001

Expression and role of functional glucocorticoid receptors in the human androgen-independent prostate cancer cell line, DU145.

We investigated the presence of glucocorticoid receptors (GR) as well as the role of glucocorticoids (Gc) in the control of proliferation of the androgen-independent prostate cancer cell line, DU145. We detected the presence of a specific high affinity binding site (K(d) 2.3 nM) for [(3)H]dexamethasone ([(3)H]Dex) in the cytosolic preparations of DU145 cells; the density of these binding sites is significantly higher than that detected in HA22T/VGH and in HepG2, two hepatoma cell lines classically considered models for the study of GR. Immunocytochemistry studies confirmed the presence of GR in the cytosolic compartment of DU145 cells; GR undergo translocation to the nucleus following exposure to dexamethasone (Dex). The functional activity of GR present in DU145 cells was also studied by analyzing the potency of Dex in inducing chloramphenicol acyltransferase (CAT) activity in DU145 cells transfected with a glucocorticoid/progesterone response element (GRE/PRE) tkCAT plasmid (GRE/PREtkCAT plasmid). The results have shown that Dex stimulates the transcriptional activity of GR in transfected DU145 cells with an EC(50) of 9.65 nM and a maximal induction of sevenfold above basal levels. Finally, a dose-dependent (IC(50) 3.14 nM) decrease of DU145 cell numbers was observed after their exposure to Dex for 4 days; this effect was counteracted by the presence of the steroid antagonist, RU486. In conclusion, the present data suggest a possible role of corticoids in the control of the growth of androgen-independent prostate cancer.

Androgens↗
PubMed2001

Hyperhomocysteinemia in myelodysplastic syndromes: specific association with autoimmunity and cardiovascular disease.

Hyperhomocysteinemia (HH) has been associated with cardiovascular and autoimmune diseases and oxidative cell damage. Myelodysplastic syndromes (MDS) are associated with autoimmunity (AI) and increased oxidative stress. We tested the association of HH and oxidative stress in 33 MDS patients, by measuring plasma homocysteine and malondialdehyde (MDA). HH was found in 42% of cases, (4/5) cases with associated cardiovascular events (CVE)(80%), and 9/15 cases with associated AI (60%). Thus in MDS, HH was significantly associated with AI/CVE (chi(2) : p=0.0011), and this association seems to be specific, as demonstrated by the comparison of MDS presenting AI/CVE with the ischemic cardiopathy/rheumatoid arthritis control group (13/20, 65% vs 19/69, 27%; chi(2) : p=0.0021). The levels of MDA indicated increased oxidative stress. Our data may suggest that in a subset of MDS, HH may simultaneously contribute to bone marrow myelodysplasia, CVE and AI pathogenesis, possibly through oxidative cell damage.

Analysis of Variance↗
PubMed2001

Focal segmental glomerulosclerosis and hepatitis C virus: a case report.

Focal segmental glomerulosclerosis (FSGS) is a renal disease characterized by sclerotic segmentary lesions, involving a few glomeruli. Male-female ratio is >1 and, in the majority of cases, the patients are aged between 25 to 35 years. The clinical picture is similar to a nephrotic syndrome with non-selective proteinuria poorly sensitive to steroids and often associated with microhematuria. The etiology is still unknown, even in a prevalence in drug addicts, patients with AIDS and subjects with recurrent urological infections with vesico-ureteral reflux was observed. Recent reports showed that chronic infection Hepatitis C Virus (HCV)-related may be associate with or responsible for onset of some syndrome involving the kidney but not the liver. We report the case of a young woman with HCV-Ab positive chronic hepatitis that, during the disease, showed clinical findings of renal involvement, histologically related to a FSGS. We administered to her alpha-IFN at doses of 3 Mega Units thrice-a-week for six months. Serum HCV-RNA, proteinuria and hematuria disappeared simultaneously after the treatment. We underline that the lack of finding of HCV antigens or HCV-RNA in glomerular lesions (as occurred in our patient) does not rule out the virus role in pathogenesis of immunological nephritis. The recovery of our patient as well as the disappearance of proteinuria and hematuria during IFNalpha treatment may be further evidence that FSGS and chronic hepatitis HCV-related are not associated by chance. Further observations and perfectioning of diagnostic techniques are required to clarify the pathogenetic relationship between HCV and renal immunological syndromes.

Adult↗
PubMed2001

Serum lipoprotein(a) changes in acute myocardial infarction.

BACKGROUND: A strong correlation between high serum Lp(a) levels, a genetic modification of cholesterol-low density lipoproteins (c-LDL), and increased coronary heart disease rate has been found. Transient increased serum levels of this lipoprotein during acute myocardial infarction (AMI) and surgical interventions have been found. METHODS EXPERIMENTAL DESIGN: we assessed complete lipidic pattern in a study series composed of 19 patients with AMI. We also evaluated the changes of Lp(a) serum levels within the first week of the disease in order to assess whether a correlation between this parameter and extent of necrotic myocardial area is present. PATIENTS: study series was made up of 19 patients (13 males, 6 females; mean age 57.94+/-10.7 years) with AMI compared to 25 control subjects (12 males and 13 females; mean age 51.12+/-15.34 years). MEASURES: we also withdrew a blood sample on days 1, 3 and 7 from the onset of the AMI. On the first day we evaluated the serum levels of the following parameters: glycaemia, azotemia, creatininemia, urycaemia, total cholesterol, high density lipoprotein cholesterol (c-HDL), low density lipoprotein cholesterol (c-LDL), triglycerides, fibrinogen, creatinphosphokinase, aspartate aminotranspherase, thromboplastine time and prothrombinic activity. Lp(a) has been evaluated on day 1, 3 and 7 and after 6 months from AMI. We performed an ultrasound scanning (US) of the heart in day 7 for evaluation of the extent of necrotic myocardial area by observation of "segmental kinetic area". RESULTS: Mean basal Lp(a) serum level was 28.94+/-29.78 mg/dl (as median 17), (normal values 0 to 25 mg/dl). This value was not changed on day 3 (mean 29.47+/-30.46 mg/dl, median 18), while significantly increased on day 7 (39.84+/-42.77, median 26, p=0.05). Spearman's rank correlation test showed a strong correlation between the increase of Lp(a) serum levels on day 7 and extent of necrotic myocardial area (r=0.696, p=0.001). CONCLUSIONS: The positive correlation between mean Lp(a) values on day 1 and 7, and the size of the necrotic area, suggest that Lp(a) has an atherogenic and prothrombotic role. Moreover, elevated Lp(a) values were related to greater tissue damage. We believe that periodical determination of Lp(a) values in subjects with coronary disease is useful in order to predict further acute vascular events.

Aged↗
PubMed2001

Lipoprotein (a) behaviour in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignancy representing in Europe the 3-5% of all malignant tumors. Metabolic pathway of Lipoprotein(a) [Lp(a)] is influenced by various cytokines delivered during inflammatory and neoplastic diseases. Liver seems to be the main site of Lp(a) synthesis. METHODS: A group of patients affected by HCC was studied in order to evaluate the changes in serum Lp(a) levels and their significance. PARTICIPANTS: 40 patients (25 males and 15 females) affected by primary HCC and 25 control healthy subjects (12 males and 13 females). In HCC patients we evaluated the following serological parameters: Lp(a), total cholesterol (TC), LDL-Cholesterol (LDL-C), HDL-Cholesterol (HDL-C), triglycerides (TG), albumin, (pseudo)cholinesterase (CHE), aspartate amino-transpeptidase (AST), alanine amino-transpeptidase (ALT), gamma-glutamyl transpeptidase (g-GT), alkaline phosphatase (ALP), ferritin, alpha fetoprotein, partial thromboplastin time (PTT), Quick time, prothrombinic activity (PA) and fibrinogen. Statistical analysis of the data obtained was performed using the variance analysis (ANOVA method) and Student's OtO for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. RESULTS: In patients with HCC, mean serum TC, LDL-C TG and Lp(a) levels were significantly lower than in controls. HDL-C did not show a statistically significant difference between the two groups studied. Furthermore, we found a positive correlation between: Lp(a) and CHE, Lp(a) and albumin, CHE and LDL-C; while a negative correlation has been found between: Lp(a) and alpha-fetoprotein, Lp(a) and ferritin, CHE and alpha-fetoprotein. CONCLUSIONS: On the basis of the relationship with alfa fetoprotein and ferritin serum levels, Lp(a) seems to represent an indirect index of liver damage. Lp(a) is a risk factor for vascular diseases and seems to have an interesting role in the liver functions. We conclude that the evaluation of Lp(a) serum levels may contribute, among other markers, to a more complete evaluation of the liver function in patients with HCC suggesting a predictive role for this lipoprotein.

Aged↗
PubMed2001

[Mepartricine and prostatitis. Clinical experience and rationale for use].

BACKGROUND: The purpose of this study was to report our experience on the use of Mepartricine in the treatment of chronic and sub-acute prostatitis and to analyse, on the basis of the literature, the role of estrogens, the target of Mepartricine in the development and maintenance of prostatic inflammatory reactions. METHODS: In a retrospective study the data of 110 patients who presented with lower urinary tract symptoms suggestive of prostatitis, from January 1994 to February 1999 have been evaluated: 65 of this patients had an abacterial prostatitis, and 45 a bacterial prostatitis. The Mearers-Stamey test was used to localize inflammation and pathogens to prostate. The clinical symptoms presented were essentially pelvic and perineal pain and irritative and obstructive voiding symptoms. The treatment was based on antibiotic therapy indicated by the sensitivity to antibiotic assay. In abacterial prostatitis, in cases of Chlamidia, Mycoplasma and Ureaplasma positivity, the treatment was based on macrolides and tetracycline use. All the patients received Mepartricine by oral supply, 1 daily tablet (40 mg) for 60 days. RESULTS: After two months of treatment remarkable improvements in symptoms were obtained despite the persistent bacteriological positivity in the prostatic secretion in 68% of cases. Therefore antinflammatory antiedemic and decongestant effects of Mepartricine on prostatic inflammation, are observed. CONCLUSIONS: The data of the literature show data estrogens modulate inflammatory reactions: it is possible that their decrease can produce, at prostatic level, antinflammatory effects improving urethro-prostatic bladder functions. Personal experience seems to confirm this supposition and so we think that Mepartri-cine can be considered and excellent coadjuvant in the treatment of prostate inflammation, independent of etiology.

Adult↗
PubMed2000

Growth-inhibitory activity of melatonin on human androgen-independent DU 145 prostate cancer cells.

BACKGROUND: The pineal hormone melatonin has been shown to exert a direct oncostatic activity on neoplastic cells, particularly from breast cancer. In the present study, we evaluated the effects of melatonin on the proliferation and on the cell cycle distribution of human androgen-independent DU 145 prostate cancer cells. Experiments were also performed to gain insights into the possible mechanism of action of the hormone. METHODS: The effects of melatonin on DU 145 cell proliferation was analyzed by counting the cells by hemocytometer at the end of treatment. The effects of the pineal hormone on cell cycle distribution were evaluated by FACS analysis. RT-PCR studies were performed to detect Mel(1a) and Mel(1b) expression in DU 145 cells. The cellular localization of (125)I-melatonin binding sites was investigated by radioreceptor assay. A commercially available binding-protein assay kit was utilized to evaluate intracellular cAMP levels. RESULTS: Melatonin, in physiological doses, significantly inhibited DU 145 cell proliferation and induced cell cycle withdrawal by accumulating cells in G0/G1 phase. The mRNA for Mel(1a) receptors was found to be expressed in DU 145 cells; however, by radioreceptor assay, no binding sites for (125)I-melatonin could be detected in membrane preparations, suggesting that, in these cells, the level of translation of this mRNA is too low to possibly mediate the antiproliferative action of the hormone. In agreement with this hypothesis, melatonin did not affect forskolin-induced intracellular cAMP accumulation. Binding sites for (125)I-melatonin were found in nuclear extracts of DU 145 cells. CONCLUSIONS: Melatonin exerts a direct oncostatic activity on human androgen-independent prostate cancer cells, by affecting cell cycle progression. This activity seems to be mediated by nuclear, but not by membrane, receptors.

Cell Cycle↗