Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well as in young men (YM, n = 10). Simultaneously, the pituitary hormones prolactin, growth hormone, luteinizing hormone and follicle-stimulating hormone were measured by RIA. All subjects were untreated and free of serious complaints, and they stayed in the same environment. The data were analyzed by the population mean-cosinor method, and linear correlation coefficients between the five hormones were calculated for each group. Melatonin showed significant circadian rhythms in young men and patients with BPH and PCi but not in patients with PC. Twenty-four-hour mean concentration (mesor) and amplitude were significantly increased in patients with PCi as compared to patients with PC. Prolactin showed significant circadian rhythms in young men and in patients with BPH, whereas patients with PCi and PC appeared to have ultradian variations. Growth hormone did not show significant rhythms in any of the groups; the mesors were elevated in all tumor groups as compared to young men. Gonadotropin mesors were elevated in all tumor patients as compared to young men; rhythms were not detected. Carcinoma patients showed different interhormonal correlations than all other groups. These results indicate that modulation of melatonin secretion, accompanied by changes in the pituitary hormone levels, may be related to development and growth of prostate cancer.
J Pineal Res 1985
PMID:Evidence for modulation of melatonin secretion in men with benign and malignant tumors of the prostate: relationship with the pituitary hormones. 242 Sep 60

Conventional antiandrogen therapy for prostatic cancer generally results in the death of androgen-dependent cells, resulting in shrinkage of the tumor, followed by regrowth of the tumor as androgen-insensitive cells take over. Because of reported antigonadotropic and antineoplastic effects of the pineal hormone melatonin (MEL), we hypothesized that this indole might provide an effective therapy for prostate cancer, as it would be effective against both populations of tumor cells. We used three sublines of the Dunning R3327 rat prostatic adenocarcinoma to determine whether MEL could suppress the growth of these tumors and, if so, by what mechanisms this occurs. In one experiments, we compared the growth of a well-differentiated slow-growing Dunning tumor in rats given MEL combined with the potentiating procedure olfactory bulbectomy (BULBX), with that in rats pinealectomized (PINX) or untreated. Tumor growth in BULBX-MEL rats was significantly suppressed over that in the other two groups, as were the weights of the gonads and accessory sex glands. Tumor morphology, DNA concentration, and androgen receptor concentration and distribution were identical in untreated controls and in BULBX-MEL rats, suggesting that the treatment affected all populations of tumor cells equally. With another strain of well-differentiated slow-growing Dunning tumor, we examined the effects of MEL in rats with and without BULBX. Reproductive parameters were not suppressed in BULBX-MEL rats and, while there was a trend toward slower tumor growth in this group, this was not significant. Intact rats given MEL grew larger tumors than did control rats but, again, differences were not significant. In a third experiment, we examined a fast-growing androgen-insensitive anaplastic Dunning tumor. PINX was without effect on this tumor, but BULBX-MEL resulted in a significant suppression of one of the constants in the logistic equation fitted to the growth curves. This indicates that there were some direct antitumor effects of BULBX-MEL on this tumor strain. We conclude that MEL suppresses growth of some Dunning tumor strains.
J Pineal Res 1987
PMID:Effects of olfactory bulbectomy, melatonin, and/or pinealectomy on three sublines of the Dunning R3327 rat prostatic adenocarcinoma. 362 64

Melatonin, a pineal secretory product, has been shown to exert a direct anti-proliferative action on the androgen-sensitive LNCaP prostate cancer cell line through hitherto undefined mechanisms. In this communication, expression of mt1 melatonin receptor protein in human prostate cancer tissues and LNCaP cells was demonstrated by immunohisto(cyto)chemistry and western blotting, hence supporting the use of LNCaP cell line as a model for the study of melatonin signaling in prostate cancer cell growth. Using 3H-thymidine incorporation assay, LNCaP cell proliferation was inhibited by 2-iodomelatonin, a high-affinity melatonin receptor agonist. Furthermore, melatonin inhibited 3H-thymidine incorporation into LNCaP cells and attenuated 5alpha-dihydrotestosterone (DHT) or 17beta-estradiol (E2)-induced stimulation of LNCaP cell proliferation at physiological and pharmacological concentrations. Similar concentration-dependent inhibition of sex steroid-induced stimulation of thymidine incorporation into LNCaP cells by 2-iodomelatonin was also observed. Interestingly, attenuation of sex steroid-stimulated calcium influx into LNCaP cells by pharmacological concentrations of melatonin was recorded, whereas 2-iodomelatonin had no effect on cytosolic calcium changes induced by sex steroids. In addition, proliferative and cytosolic calcium changes were associated with inhibition of total prostate-specific antigen (PSA) production by LNCaP cells at high physiological and pharmacological concentrations of melatonin. Our data suggest that activated mt1 receptor and attenuated sex steroid-induced calcium influx are two important mechanisms mediating the direct anti-proliferative action of melatonin on androgen-responsive human prostate cancer cells.
J Pineal Res 2000 Oct
PMID:Potential involvement of mt1 receptor and attenuated sex steroid-induced calcium influx in the direct anti-proliferative action of melatonin on androgen-responsive LNCaP human prostate cancer cells. 1103 15

Melatonin inhibited the proliferation of hormone-independent LNCaP prostate cancer cells partly via MT1 receptor activation both in vitro and in nude mice xenograft model. In this study, the melatonin receptor expression in the prostate cancer tissue of a patient with bone metastases and the effect of melatonin on the biochemical progression of hormone-refractory prostate tumor which later developed in the same patient were reported. Saturation and competition 2-[125I]iodomelatonin binding assays were conducted on prostate tumor tissue obtained by transurethral resection of the prostate from the index patient. The receptor subtype identity of melatonin receptor expressed in the cancer tissue was determined by comparison of the rank order of inhibition constants (Ki) of various melatonergic ligands and the affinity of 4-phenyl-2-propionamidotetraline relative to melatonin in inhibiting 2-[125I]iodomelatonin binding to the tumor sample and to human cell lines stably transfected with MT1 or MT2 melatonin receptor subtype. MT1 receptor expression in the cancer tissue was also examined by immunohistochemistry. The surgically castrated patient later developed biochemical relapse of his disease. His serum total prostate-specific antigen (PSA) level was monitored before and during treatment with 5 mg/day oral melatonin at 20:00 hr. High-affinity (Kd = 103.7 pm) MT1 melatonin receptor subtype was expressed by the patient's prostate cancer. As indicated by his PSA levels, melatonin induced stabilization of his hormone-refractory disease for 6 wk. This report validates melatonin's oncostatic action on prostate cancer and the potential involvement of MT1 receptor subtype in the attendant antiproliferative signal transduction as suggested by recent preclinical laboratory findings in a human.
J Pineal Res 2003 Oct
PMID:Melatonin slowed the early biochemical progression of hormone-refractory prostate cancer in a patient whose prostate tumor tissue expressed MT1 receptor subtype. 1293 1

Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK-N-MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6-diamidino-2-phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase-3 activation. Cell death was dose and time-dependent; the lowest effective concentration of melatonin was 100 microm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.
J Pineal Res 2006 Sep
PMID:Melatonin induces apoptosis in human neuroblastoma cancer cells. 1687 18

There is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone-refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT(1) receptor expression in prostate cancer. The aim of this study was to determine, using a pharmacological approach, the signaling mechanisms of melatonin in hormone-refractory 22Rv1 human prostate cancer cell antiproliferation. Both immunoreactive MT(1) and MT(2) subtypes of G protein-coupled melatonin receptor were expressed in 22Rv1 cells. Melatonin inhibited, concentration dependently, cell proliferation, upregulated p27(Kip1) gene transcription and protein expression, and downregulated activated androgen signaling in 22Rv1 cells. While the effects of melatonin were mimicked by 2-iodomelatonin, a high-affinity nonselective MT(1) and MT(2) receptor agonist, melatonin effects were blocked by luzindole, a nonselective MT(1) and MT(2) receptor antagonist, but were unaffected by 4-phenyl-2-propionamidotetraline, a selective MT(2) receptor antagonist. Importantly, we discovered that the antiproliferative effect of melatonin exerted via MT(1) receptor on p27(Kip1) gene and protein upregulation is mediated by a novel signaling mechanism involving co-activation of protein kinase C (PKC) and PKA in parallel. Moreover, we also showed that a melatonin/MT(1)/PKC mechanism is involved in melatonin-induced downregulation of activated androgen signal transduction in 22Rv1 cells. Taken together with the known molecular mechanisms of prostate cancer progression and transition to androgen independence, our data provide strong support for melatonin to be a promising small-molecule useful for prostate cancer primary prevention and secondary prevention of the development and progression of hormone refractoriness.
J Pineal Res 2007 Mar
PMID:Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: implications for prostate cancer chemoprevention. 1728 52

Prostate cancer is a public health problem of the elderly men. It has been estimated that one in six men will develop prostate cancer in his lifetime in the USA. There is thus a huge clinical demand for effective therapies for the prevention and treatment of the disease. Here, the scientific evidence supporting the effectiveness of melatonin in inhibiting the development and progression of prostate cancer is reviewed. The rational use of melatonin in prostate cancer prevention, stabilization of clinically localized favourable-risk prostate cancer and palliative treatment of advanced or metastatic tumour is discussed within the context of the molecular pathogenesis of the disease.
J Pineal Res 2007 Aug
PMID:Towards rational and evidence-based use of melatonin in prostate cancer prevention and treatment. 1822 13

Melatonin, an indole mainly synthesized in the pineal gland during the dark phase, plays a role as an endogenous antioxidant and an anticancer agent in many tumors. Melatonin, at pharmacological concentrations, inhibits cell growth and induces neuroendocrine differentiation in prostate cancer cells. Classically it has been considered that melatonin enters freely into most of cells by passive diffusion through the cell membrane; however, there are few studies examining how melatonin is taken up by cancer cells. The aim of the present paper was to study the uptake of melatonin into human androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cells. Increased concentrations of melatonin induced a rapid and transitory rise in intracellular melatonin content in both cell types, with a peak of maximal content at 6 hr after melatonin addition, following a rhythmic uptake; melatonin was found in both cytoplasm and nuclear fractions. Inhibition of protein or RNA synthesis partially blocked melatonin uptake in both cell lines. Interestingly, melatonin pulse incubation led to a higher uptake after four cycles of pulse incubation. Neither extracellular Ca(2+)/K(+) alterations nor the presence of bovine serum albumin or charcoal-stripped serum modified the profile of melatonin uptake. On the contrary, chemical binding of melatonin to BSA totally prevented melatonin from entering into cells. The present data support the hypothesis that a facilitated diffusion or an active process rather than simple passive diffusion through the cell membrane is the major mechanism in melatonin uptake by prostate cancer cells and it accounts for its intracellular concentration (350 nM-3.3 microM), which is related to its anti-tumor actions.
J Pineal Res 2008 Oct
PMID:Melatonin uptake in prostate cancer cells: intracellular transport versus simple passive diffusion. 1834 16

The role of antioxidants in reducing cancer initiation and progression has been highlighted in recent years. Not only antioxidants limit cancer cell growth but also, in some situations, they promote the effectiveness of conventional treatments. Melatonin, an endogenously synthesized antioxidant, reduces cell growth of several tumor types both in vivo and in vitro. Additionally, the indole limits the collateral damage induced by many chemotherapeutic agents. By using a cellular model of human prostate cancer, we studied the ability of melatonin to enhance apoptosis induced by tumor necrosis factor or gamma radiation. It has been reported that melatonin reduces prostate cancer cell growth and, more recently, it promotes cell differentiation. In this work, we also show that melatonin elevates p21 protein levels and increases antioxidant capacity of prostate cancer cells. In addition, melatonin significantly enhances hrTNFalpha induced cell death by decreasing NFkappaB activation. Bcl-2 and survivin down-regulation appears to be associated to apoptosis stimulation under NFkappaB inhibition. On the contrary, melatonin does not promote irradiation-induced cell death due to an increment in intracellular glutathione content. In conclusion, prevention of NFkappaB activation by melatonin enhances the effectiveness of cytokine treatment in prostate cancer cells but it is not sufficient to enhance cell death triggered by other therapies which generate free radicals. A crucial role of glutathione in survival mechanisms of prostate cancer cells should be carefully considered.
J Pineal Res 2008 Oct
PMID:Critical role of glutathione in melatonin enhancement of tumor necrosis factor and ionizing radiation-induced apoptosis in prostate cancer cells in vitro. 1838 30

Circannual variation in the human serum levels of prostate-specific antigen, a growth marker of the prostate gland, has been reported recently. The present study was conducted to investigate the role of the photoperiodic hormone melatonin (MLT) and its membrane receptors in the modulation of human prostate growth. Expression of MT(1) and MT(2) receptors was detected in benign human prostatic epithelial tissues and RWPE-1 cells. MLT and 2-iodomelatonin inhibited RWPE-1 cell proliferation and up-regulated p27(Kip1) gene and protein expression in the cells. The effects of MLT were blocked by the nonselective MT(1)/MT(2) receptor antagonist luzindole, but were not affected by the selective MT(2) receptor antagonist 4-phenyl-2-propionamidotetraline. Of note, the antiproliferative action of MLT on benign prostate epithelial RWPE-1 cells was effected via increased p27(Kip1) gene transcription through MT(1) receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel, a signaling process which has previously been demonstrated in 22Rv1 prostate cancer cells. Taken together, the demonstration of the MT(1)/PKA+PKC/p27(Kip1) antiproliferative pathway in benign and malignant prostate epithelial cell lines indicated the potential importance of this MLT receptor-mediated signaling mechanism in growth regulation of the human prostate gland in health and disease. Collectively, our data support the hypothesis that MLT may function as a negative mitogenic hormonal regulator of human prostate epithelial cell growth.
J Pineal Res 2008 Nov
PMID:Melatonin as a negative mitogenic hormonal regulator of human prostate epithelial cell growth: potential mechanisms and clinical significance. 1863 86


1 2 3 Next >>