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

Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.
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PMID:The effects of cyclooxygenase-2 inhibitors on urological cancer cells. 1513 13

Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.
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PMID:Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells. 1545 72

Although p53-inactivating mutations have been described in the majority of human cancers, their role in prostate cancer is controversial as mutations are uncommon, particularly in early lesions. p53 is activated by hypoxia and other stressors and is primarily regulated by the Mdm2 protein. Cyclooxygenase (COX)-2, an inducible enzyme that catalyzes the conversion of arachidonic acid to prostaglandins and other eicosanoids, is also induced by hypoxia. COX-2 and resultant prostaglandins increase tumor cell proliferation, resistance to apoptosis, and angiogenesis. Previous reports indicate a complex, reciprocal relationship between p53 and COX-2. To elucidate the effects of COX-2 on p53 in response to hypoxia, we transfected the COX-2 gene into the p53-positive, COX-2-negative MDA-PCa-2b human prostate cancer cell line. The expression of functional p53 and Mdm2 was compared in COX-2+ versus COX-2- cells under normoxic and hypoxic conditions. Our results demonstrated that hypoxia increases both COX-2 protein levels and p53 transcriptional activity in these cells. Forced expression of COX-2 increased tumor cell viability and decreased apoptosis in response to hypoxia. COX-2+ cells had increased Mdm2 phosphorylation in either normoxic or hypoxic conditions. Overexpression of COX-2 abrogated hypoxia-induced p53 phosphorylation and promoted the binding of p53 to Mdm2 protein in hypoxic cells. In addition, COX-2-expressing cells exhibited decreased hypoxia-induced nuclear accumulation of p53 protein. Finally, forced expression of COX-2 suppressed both basal and hypoxia-induced p53 transcriptional activity, and this effect was mimicked by the addition of PGE2 to wild-type cells. These results demonstrated a role for COX-2 in the suppression of hypoxia-induced p53 activity via both direct effects and indirect modulation of Mdm2 activity. These data imply that COX-2-positive prostate cancer cells can have impaired p53 function even in the presence of wild-type p53 and that p53 activity can be restored in these cells via inhibition of COX-2 activity.
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PMID:Cyclooxygenase-2 suppresses hypoxia-induced apoptosis via a combination of direct and indirect inhibition of p53 activity in a human prostate cancer cell line. 1555 Apr

The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyretic properties of COX-2 selective inhibitors. The coxibs rofecoxib and celecoxib have been introduced into therapy and seem to offer some advantages over the classical non-selective NSAIDs. The search for new COX-2 inhibitors is going on, the development of etoricoxib and lumiracoxib is a step ahead concerning efficacy, tolerability and safety. Until today COX-2 selective inhibitors have found their place in therapy of arthritis, osteoarthritis, dysmenorrhea and acute pain. A new paradigm in pain therapy seems to justify their use in perioperative settings in a preemptive or multimodal therapeutical strategy. In the future COX-2 selective inhibitors as opioid sparing agents could become an important tool in pain therapy. Even a therapeutical benefit of COX-2 selective inhibitors in the treatment of Alzheimer's Disease or in the prevention or treatment of colorectal or prostate cancer is presently intensely investigated. Recently some authors reported on COX-3, a splicing variant of COX-1. If COX-3 really represents the target for acetaminophen must be called into question.
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PMID:Novel insights and therapeutical applications in the field of inhibitors of COX-2. 1557 5

Cyclooxygenase (COX)-2 is involved in several physiologic and pathologic processes. COX-2 is overexpressed in human and canine prostate cancer, but little is known about COX-2 inducers in the prostate. Our objective was to investigate the effect of sex steroid hormones on COX-2 expression in the canine prostate in vivo. COX-2 expression was evaluated by immunohistochemistry in intact and castrated dogs treated with exogenous androgen or estrogen. Results showed that no COX-2 staining was observed in prostates of untreated or androgen-treated castrated or intact dogs. However, treatment of intact and castrated dogs with estrogen resulted in squamous metaplasia with intense COX-2 expression observed in both squamous epithelial cells and in cells of acini without metaplasia. This is the first report to demonstrate the induction of COX-2 by estrogen in the prostate in vivo.
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PMID:Estrogen-dependent induction of cyclooxygenase-2 in the canine prostate in vivo. 1565 82

Prostate cancer is an attractive target for chemoprevention because of its ubiquity, treatment-related morbidity, long latency between premalignant lesions and clinically evident cancer, and defined molecular pathogenesis. Prevention of this disease would have a major impact on disease-associated cost, morbidity, and mortality for a large segment of the population. A major advance in prevention of prostate cancer came in 2003 with the publication of the Prostate Cancer Prevention Trial (PCPT). This overview summarizes the results of that trial, the design of other large-scale trials, and advances in understanding of the molecular mechanisms underlying the effect of other promising agents, including dutasteride, selenium, Vitamin E, Vitamin D, COX-2 inhibitors, lycopene, and green tea.
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PMID:Chemoprevention of prostate cancer. 1578 Sep 4

Prostate cancer cells are generally dependent on androgen stimulation mediated by the androgen receptor (AR) for growth and survival, and, therefore, hormonal manipulation, such as castration and/or the use of AR antagonists, results in a regression of the cancer. However, this treatment very rarely leads to the "cure" of advanced disease, and cancers eventually become androgen-independent. A number of genes/pathways have been reported to be activated in prostate cancer, most of which are possibly associated with disease progression. In this article, among them, we focus on Akt (also known as protein kinase B), cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9, whose activities or expressions have been found to be regulated by androgens/AR. Previous studies by us and others, with androgen-sensitive prostate cancer cell lines, have demonstrated that androgen deprivation results in activation/overexpression of Akt, COX-2, and MMP-9 in cells. This suggests that androgen deprivation in clinical settings activates the Akt, COX-2, and MMP-9 pathways in prostate cancer, which may increase cell growth and in turn promote the transition to the androgen-independent state. We hypothesize that androgen deprivation, in combination with inhibition of the Akt, COX-2, and MMP-9 pathways, delays the androgen-independent transition and has more beneficial effects than hormonal therapy alone.
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PMID:Inhibition of the Akt, cyclooxygenase-2, and matrix metalloproteinase-9 pathways in combination with androgen deprivation therapy: potential therapeutic approaches for prostate cancer. 1604 18

Chronic inflammation has been associated with resulting in malignancies in prostate cancer patients. In the May 2005 issue of Clinical Cancer Research, a study by Wang et al. demonstrates a relationship between COX-2 expression and the local chronic inflammation within prostate cancer and the increased angiogenesis. Confirming the existence and extent of this relationship is essential in the determination of therapeutic modalities for the prevention and treatment of prostate cancer.
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PMID:Cyclooxygenase-2 and angiogenesis in prostate cancer. 1612 81

Traditional urological concerns, such as bladder instability, bladder cancer, prostate cancer and incontinence, were focused upon. In addition, significant attention was paid to erectile dysfunction, with varied developments in the field. Capsaicin was presented as having a role to play in the reduction of bladder instability, while a new formulation of oxybutinin was shown to improve female urge incontinence. The combination of topical estrogen and an oral agonist, phenylpropanolamine, also gave significant improvement in menopausal urinary urgency and incontinence. Tetrahydropyranyladriamycin (THPA) will possibly be effective for adequate prophylaxis against the recurrence of early bladder cancer. COX-2 receptor modulation has a role in the treatment of bladder cancer, whilst the endothelin receptor antagonist ABT-627 (Abbott International Ltd) may prove effective in the treatment of prostate cancer. Melanotan II (PNU-83757; Pharmacia and Upjohn Inc) and IC-351 (Icos Corp) are new compounds for the treatment of erectile dysfunction (ED), and more light is shed on a role for apomorphine for the same indication.
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PMID:American Urological Association--94th annual meeting. 1-6 May 1999, Dallas, USA. 1612 34

Cyclooxygenase (COX) inhibitors have suppressive effects on several types of cancer cells including prostate cancer. In this study, we considered the potential COX-inhibitory activity of a unique anti-inflammatory herbal preparation (Zyflamend; New Chapter, Inc., Brattleboro, VT) and analyzed its effects on the human prostate cancer cell line LNCaP. COX inhibitory activity of Zyflamend was determined by a spectrophotometric-based assay using purified ovine COX-1 and COX-2 enzymes. Effects of Zyflamend on LNCaP cell growth and apoptosis in vitro were assessed by cell counting, Western blot detection of poly ADP-ribose polymerase (PARP) cleavage, and measurement of caspase-3 activity in treated and control cell extracts. Western blotting techniques were conducted to determine the effects of this herbal preparation on the expression of the cell signaling proteins, p21, androgen receptor (AR), phospho-protein kinase C (pPKC)(alpha/beta), and phospho (p)Stat3. The phospohorylation status of several signal transduction phosphoproteins was profiled using a high-throughput phosphoprotein screening assay in treated cells and compared to controls. Zyflamend dramatically decreased COX-1 and COX-2 enzymatic activity. Elevated p21 expression coincided with attenuated cell growth following treatment of LNCaP cells with Zyflamend. PARP cleavage fragments were evident, and caspase-3 activity was upregulated over the control indicating the ability of Zyflamend to induce apoptosis of these cells. Androgen receptor expression levels declined by 40%, and decreases were observed in the active forms of Stat3 and PKC(alpha/beta) in Zyflamend-treated LNCaP cells. Zyflamend inhibited both COX-1 and COX-2 enzymatic activities, suppressed cell growth, and induced apoptosis in LNCaP cells. However, our data suggests that the effects are likely due to COX-independent mechanisms potentially involving enhanced expression of p21 and reduced expression of AR, pStat3, and pPKC(alpha/beta).
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PMID:Zyflamend, a unique herbal preparation with nonselective COX inhibitory activity, induces apoptosis of prostate cancer cells that lack COX-2 expression. 1620 51


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