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)

Specific metabolites of estrogens, catechol estrogen-3,4-quinones, if produced in relatively large amounts, can become chemical carcinogens by reacting with DNA to form predominantly depurinating DNA adducts. Estradiol (E2)-3,4-quinone (Q) reacts with DNA to form predominantly the depurinating DNA adducts, 4-hydroxyestradiol (OHE2)-1-N3Ade and 4-OHE 2-1-N7Gua. The depurinating adducts induce mutations by error-prone repair. We have conducted a study in which selected natural chemopreventing agents, N-acetylcysteine (NAcCys), melatonin, reduced lipoic acid, and resveratrol, have been tested for their ability to prevent the reaction of E(2)-3,4-Q with DNA. When DNA was incubated with E(2)-3,4-Q or lactoperoxidase-activated 4-OHE2 in the presence of an antioxidant, the formation of the N3Ade and N7Gua adducts was reduced. E(2)-3,4-Q or lactoperoxidase-oxidized 4-OHE 2 (87 microM final concentration) was incubated with calf-thymus DNA and one of the antioxidants at different ratios (1:0, 1:0.3, 1:1, and 1:3 with respect to E(2)-3,4-Q or 4-OHE2) at 37 degrees C. After 10 h, the DNA was precipitated, and the supernatant was analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry (LC/MS/MS). As anticipated, resveratrol and melatonin did not affect the formation of the depurinating adducts when E(2)-3,4-Q was reacted with DNA in their presence. On the other hand, NAcCys and lipoic acid (reduced form) showed a significant inhibition of the formation of the depurinating adducts by E(2)-3,4-Q. With reaction of lactoperoxidase-activated 4-OHE2 with DNA, resveratrol achieved the highest level of inhibition, NAcCys and reduced lipoic acid produced moderate inhibition, and melatonin had the least inhibition. These results demonstrate that all four selected compounds can inhibit the formation of depurinating estrogen-DNA adducts and set the stage for studies of their ability to inhibit adduct formation and malignant transformation in mammary epithelial cells. This approach is highly useful for identifying agents to prevent the initiation of human cancers, especially breast and prostate cancer.
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PMID:Inhibition of depurinating estrogen-DNA adduct formation by natural compounds. 1803 13

Iron overload may increase prostate cancer risk through stimulation of oxidative stress, and endogenous pro- and antioxidant capabilities, i.e. manganese superoxide dismutase (MnSOD) and myeloperoxidase (MPO), may modify these associations. We investigated this hypothesis in the Carotene and Retinol Efficacy Trial cohort in a nested case-control study. Although there was no association between iron intake and risk overall, there was a suggestion of increased risk of clinically aggressive prostate cancer with higher iron intake [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 0.9-2.0]. Associations were most notable for men with aggressive prostate cancer who were below the median consumption of total fruits and vegetables (OR = 1.8, 95% CI = 1.1-3.2). Associations between MPO -463 G to A genotype (rs2333227) and prostate cancer risk were only noted among men with aggressive cancer, with more than a 2-fold risk reduction among men with AA genotypes (OR = 0.4, 95% CI = 0.2-1.0); MnSOD was not associated with risk overall, but the MnSOD T to C (Val-9Ala, rs4880) polymorphism modified associations between risk of clinically aggressive prostate cancer and dietary iron intake (P for interaction = 0.02). Among aggressive cancer cases with the TT genotype, higher iron intake level was associated with >2-fold increase in risk (OR = 2.3, 95% CI = 1.0-4.9), whereas there was no association among men with CC genotypes (OR = 0.9, 95% CI = 0.4-2.3). Although interactions were not significant, there were similar patterns for MPO genotype, iron intake and risk. These findings suggest that higher iron intake may be associated with risk of clinically aggressive prostate cancer, and that endogenous antioxidant capabilities may modify these associations.
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PMID:Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort. 1829 81

Prostate cancer represents a major clinical public health challenge. Both epidemiological and clinical intervention studies support the protective role of selenium against development of prostate cancer. However, the mechanisms responsible for the inhibitory activity by this micronutrient remain elusive. Furthermore, literature reports consistently have shown that the dose and form of selenium are important factors in cancer chemoprevention. Thus, in the present investigation using androgen responsive (AR) lymph node carcinoma of the prostate (LNCaP) and its androgen-independent clone (AI) LNCaP C4-2 human prostate cancer cells, we compared the effects of selenomethionine (SM) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on cell growth, DNA synthesis, and on proteomic profiles. p-XSC (5-20 microM) significantly inhibited cell growth in both cell types in a dose-dependent manner; SM was also effective but at much higher doses (50-100 microM). We hypothesize that the inhibition of cell growth is due, in part, to selenium interaction with redox-sensitive proteins. Using 2D gel electrophoresis, both organoselenium compounds altered the expression, to a varied extent, of several unrecognized selenium-responsive proteins. Employing matrix-assisted laser-desorption ionization (MALDI) and time-of-flight (TOF; MALDI-TOF) followed by tandem mass spectrometric analysis, we identified the following proteins: cofilin-2, heterogeneous nuclear ribonucleoprotein, single-stranded mitochondrial DNA binding protein, chaperonin 10, nucleoside diphosphate kinase 6, and chain A Horf 6 human peroxidase enzyme. This is the first report showing that SM and p-XSC are capable of altering these proteins; their roles in prostate cancer prevention warrant further investigations.
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PMID:Effects of naturally occurring and synthetic organoselenium compounds on protein profiling in androgen responsive and androgen independent human prostate cancer cells. 1844 60

Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (approximately 90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.
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PMID:Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. 1863 53

Nitric oxide ((.)NO) induces apoptosis at high concentrations by S-nitrosating proteins such as glyceraldehyde-3-phosphate dehydrogenase. This literature analysis revealed that failure to sustain high (.)NO concentrations is common to all cancers. In cervical, gastric, colorectal, breast, and lung cancer, the cause of this failure is the inadequate expression of inducible nitric oxide synthase (iNOS), resulting from the inhibition of iNOS expression by TGF-beta1 at the mRNA level. In bladder, renal, and prostate cancer, the reason for the insufficient (.)NO levels is the depletion of arginine, resulting from arginase overexpression. Arginase competes with iNOS for arginine, catalyzing its hydrolysis to ornithine and urea. In gliomas and ovarian sarcomas, low (.)NO levels are caused by inhibition of iNOS by N-chlorotaurine, produced by infiltrating neutrophils. Stimulated neutrophils express myeloperoxidase, catalyzing H2O2 oxidation of Cl- to HOCl, which N-chlorinates taurine at its concentration of 19 mM in neutrophils. In squamous cell carcinomas of the skin, ovarian cancers, lymphomas, Hodgkin's disease, and breast cancers, low (.)NO concentrations arise from the inhibition of iNOS by N-bromotaurine, produced by eosinophil-peroxidase-expressing infiltrating eosinophils. Eosinophil peroxidase catalyzes the H2O2 oxidation of Br- to HOBr, which N-brominates taurine to N-bromotaurine at its concentration of 15 mM in eosinophils. In microvascularized tumors, the (.)NO concentration is further depleted; (.)NO is rapidly consumed by red blood cells (RBCs) through S-nitrosation of RBC glutathione and hemoglobin, and by oxidation to nitrate by RBC oxyhemoglobin. Angiogenesis-inhibiting antibodies are currently used to treat cancers; their mode of action is not, as previously thought, reduction of the tumor O2 or nutrient supply. They actually decrease the loss of (.)NO to RBCs.
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PMID:Apoptosis-inducing high (.)NO concentrations are not sustained either in nascent or in developed cancers. 1875 45

Corpora amylacea (CA) are a frequent microscopic finding in radical prostatectomy specimens from men undergoing treatment for prostate cancer. Although often observed histologically to be associated with inflammation, the contribution of CA to prostatitis-related symptoms of unknown etiology or to prostate carcinogenesis remains unclear. Prostatic calculi (PC), which potentially represent calcified forms of CA, are less common but can cause urological disease including urinary retention and prostatitis. We conducted a comprehensive compositional analysis of CA/PC to gain insight into their biogenesis. Infrared spectroscopy analysis of calculi collected from 23 patients confirmed a prevalence of calcium phosphate in the form of hydroxyapatite. This result sets PC apart from most urinary stones, which largely are composed of calcium oxalate. Tandem mass spectrometry-based proteomic analysis of CA/PC revealed that lactoferrin is the predominant protein component, a result that was confirmed by Western blot analysis. Other proteins identified, including calprotectin, myeloperoxidase, and alpha-defensins, are proteins contained in neutrophil granules. Immunohistochemistry (IHC) suggested the source of lactoferrin to be prostate-infiltrating neutrophils as well as inflamed prostate epithelium; however, IHC for calprotectin suggested prostate-infiltrating neutrophils as a major source of the protein, because it was absent from other prostate compartments. This study represents a definitive analysis of the protein composition of prostatic CA and calculi and suggests that acute inflammation has a role in their biogenesis--an intriguing finding, given the prevalence of CA in prostatectomy specimens and the hypothesized role for inflammation in prostate carcinogenesis.
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PMID:Acute inflammatory proteins constitute the organic matrix of prostatic corpora amylacea and calculi in men with prostate cancer. 1920 53

The epithelial-mesenchymal transition (EMT) is considered a key step in tumor progression, where the invasive cancer cells change from epithelial to mesenchymal phenotype. During this process, a decrease or loss in adhesion molecules expression and an increase in migration molecules expression are observed. The aim of this work was to determine the expression and cellular distribution of syndecan-1 and -2 (migration molecules) and E-cadherin and beta-catenin (adhesion molecules) in different stages of prostate cancer progression. A quantitative immunohistochemical study of these molecules was carried out in tissue samples from benign prostatic hyperplasia and prostate carcinoma, with low and high Gleason score, obtained from biopsies archives of the Clinic Hospital of the University of Chile and Dipreca Hospital. Polyclonal specific antibodies and amplification system of estreptavidin-biotin peroxidase and diaminobenzidine were used. Syndecan-1 was uniformly expressed in basolateral membranes of normal epithelium, changing to a granular cytoplasmatic expression pattern in carcinomas. Syndecan-2 was observed mainly in a cytoplasmatic granular pattern, with high immunostaining intensity in areas of low Gleason score. E-cadherin was detected in basolateral membrane of normal epithelia showing decreased expression in high Gleason score samples. beta-Catenin was found in cell membranes of normal epithelia changing its distribution toward the nucleus and cytoplasm in carcinoma samples. We concluded that changes in expression and cell distribution of E-cadherin and beta-catenin correlated with the progression degree of prostate adenocarcinoma, suggesting a role of these molecules as markers of progression and prognosis. Furthermore, changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the EMT and tumor progression of prostate cancer.
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PMID:The expression of syndecan-1 and -2 is associated with Gleason score and epithelial-mesenchymal transition markers, E-cadherin and beta-catenin, in prostate cancer. 1945 Sep 93

Biotransformation of dihydroresveratrol by crude Momordica charantia peroxidase provided six new acyclic bis[bibenzyls] 1-6. Their structures were established on the basis of NMR and MS analyses as C-C, C-O-C, and C-CH(2)-C dimers of dihydroresveratrol. Compounds 1-6 were tested for antiproliferative activity against human prostate cancer PC3 cell line in vitro, and 2 and 6 were found to be more potent than the parent compound.
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PMID:Biocatalytic production of acyclic bis[bibenzyls] from dihydroresveratrol by crude Momordica charantia peroxidase. 1969 37

Protein arrays that measure multiple protein cancer biomarkers in clinical samples hold great promise for reliable early cancer detection. Herein, we report a prototype 4-unit electrochemical immunoarray based on single-wall carbon nanotube forests for the simultaneous detection of multiple protein biomarkers for prostate cancer. Immunoarray procedures were designed to measure prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), platelet factor-4 (PF-4), and interleukin-6 (IL-6) simultaneously in a single serum sample. All of these proteins are elevated in serum of patients with prostate cancer, but they have widely different relative levels of serum concentration. Horseradish peroxidase (HRP) was used as label on detection (secondary) antibodies in a sandwich immunoassay scheme. Biotinylated secondary antibodies (Ab(2)) that bind specifically to streptavidin-HRP conjugates provided 14-16 labels per antibody and gave the necessary higher sensitivity required for PF-4 and IL-6 detection at physiological levels. Conventional singly labeled Ab(2)-HRP conjugates were sufficient for PSA and PSMA detection. Immunoarrays were used to measure four biomarkers in clinical human serum samples of prostate cancer patients and controls with excellent correlation to referee enzyme-linked immunosorbent (ELISA) assays.
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PMID:Single-wall carbon nanotube forest arrays for immunoelectrochemical measurement of four protein biomarkers for prostate cancer. 1977 54

Indole-3-acetic acid (IAA) has recently shown anticancer activity in combination with horseradish peroxidase. The current study demonstrated that IAA irradiated with ultraviolet B (IAA(UVB)) is able to generate free radicals and induce cell death in a time-dependent fashion in PC-3 prostate cancer cells, while PC-3 cells treated with IAA alone exhibited no toxic responses. It was also found through Western blot analysis that the cytotoxic effect of IAA(UVB) resulted from apoptosis. Treatment with IAA(UVB) for 24 hours showed a significant increase in phosphorylated p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, the stress signaling proteins. Furthermore, pro-caspases (-3, -8, and -9) were clearly down-regulated and poly(ADP-ribose) polymerase cleavages were demonstrated in the group treated with IAA(UVB). Flow cytometric analysis also demonstrated the induction of apoptosis by IAA(UVB) in PC-3 cells. In conclusion, this study demonstrated that IAA induced cell death in combination with UVB irradiation by increasing apoptosis in PC-3 cells.
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PMID:UVB-activated indole-3-acetic acid induces apoptosis of PC-3 prostate cancer cells. 2111 13


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