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)

The authors have studied DNA base damage and activities of antioxidant enzymes in human benign prostatic hyperplasia (BPH) tissues and surrounding disease-free tissues removed from prostate glands of 15 patients. In these tissues, endogenous levels of various typical hydroxyl radical-induced products of DNA bases and activities of catalase and superoxide dismutase were measured. The majority of patients had higher levels of DNA base lesions and lower activities of enzymes in BPH tissues than in normal prostate tissues. When activities of both enzymes were lower in BPH tissues than in normal tissues, the increases in the amounts of DNA base lesions over control levels were most prominent. In the case of similar enzyme activities in both BPH and normal tissues, no changes in levels of DNA base lesions were observed. These results suggest a possible association between antioxidant enzyme activities and levels of DNA base lesions in BPH tissues. Some of the identified DNA lesions are known to be premutagenic and may play a role in carcinogenesis. Although a possible link between BPH and prostate cancer is controversial, BPH patients with both decreased antioxidant enzyme activities and increased levels of DNA lesions may be at risk of developing prostate cancer.
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PMID:DNA base modifications and antioxidant enzyme activities in human benign prostatic hyperplasia. 753 80

The antioxidant enzymes catalase, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined in the androgen-response LNCaP and androgen-nonresponsive PC-3 and DU 145 cells as well as in prostatic epithelial cell cultures of benign and malignant human prostatic tissue. There were no differences between the enzyme activities of the human primary cell cultures from cancerous tissue and their normal counterparts. The enzyme activities of the three permanent cell lines were either higher (SOD, catalase, GR) or lower (GST, GPx) than in the primary cell cultures. In LNCaP cells catalase and GR were significantly higher, GST, in contrast, was significantly lower than in PC-3 and DU 145 cells. GST in PC-3 and DU 145 cells, and SOD in all the three cell lines showed no significant differences. Catalase, GPx and GR values were significantly different in the three permanent cell lines. The different enzymatic equipment of the prostate cancer cell lines provides the basis for experimental testing of new concepts of cancer treatment with the help of systematic modulations of the antioxidant defence systems in prostate cancer.
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PMID:Antioxidant enzymes in malignant prostate cell lines and in primary cultured prostatic cells. 916 5

Studies have described the protective role of vitamin C (ascorbic acid) in certain types of cancer. In this study, we report the effects of vitamin C treatment of two androgen independent prostate cancer cell lines from human (PC3) and rat (Mat-Ly-Lu or MLL) sources. In vitro treatment of PC3 and MLL with sodium ascorbate acid (0-10 mM) resulted in a decrease in cell viability and thymidine incorporation into DNA. These effects of vit. C were dose and time dependent. Ascorbate induced these changes through the production of hydrogen peroxide since addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbate on these cell lines. In contrast, superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide did not prevent ascorbate-induced changes emphasizing the involvement of reactive oxygen species (ROS) in cellular damage. That singlet oxygen scavengers such as sodium azide and hydroquinone, hydroxyl radical scavengers such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbate on thymidine incorporation suggests that these free radicals are not involved in cellular damage. In conclusion, these results suggest that vitamin C inhibits tumor growth by virtue of producing reactive oxygen species. These results suggest that ascorbate is a potent anticancer agent for prostate cancer cells.
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PMID:Effect of vitamin C on androgen independent prostate cancer cells (PC3 and Mat-Ly-Lu) in vitro: involvement of reactive oxygen species-effect on cell number, viability and DNA synthesis. 992 64

In this study, lipid peroxide and total sulfhydryl contents and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were investigated in the plasma of patients with benign prostatic hyperplasia (BPH) and prostate cancer. No significant change was found in lipid peroxidation or antioxidant systems in the plasma of patients with BPH and prostate cancer. The results indicate that evaluation of the prooxidant-antioxidant balance in the plasma of BPH and prostate cancer patients cannot be used as a marker to discriminate between these diseases.
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PMID:Antioxidant enzyme activities and lipid peroxides in the plasma of patients with benign prostatic hyperplasia or prostate cancer are not predictive. 1039 60

The purpose of the present study was to determine whether manganese superoxide dismutase (MnSOD) overexpression in DU145 human prostate carcinoma cells affected cell reduction-oxidation state (cell redox) and to correlate changes in cell redox status with cell cycle progression and plating efficiency. One MnSOD-overexpressing cell line had no change in other antioxidant enzymes (AEs) (nonadapted clone), whereas a second MnSOD-overexpressing cell line studied had an increase in catalase (CAT) activity (adapted clone). Correlation of biochemical studies with cell cycle studies suggested that heteroploidy observed in the nonadapted MnSOD-overexpressing cell line may be due to increased intracellular peroxides with resultant disruption of the microtubule network, while a decreased mitotic rate was associated with decreased ATP levels in mitosis. In contrast, the decrease in cell growth in the adapted cell line was demonstrated to be due to a decrease in plating efficiency. Our results demonstrate complex effects of AE imbalance on cell growth of DU145 prostate cancer cells.
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PMID:Two distinct mechanisms for inhibition of cell growth in human prostate carcinoma cells with antioxidant enzyme imbalance. 1040 22

The adult rat ventral prostate, which has been used extensively as a model for hormone-dependent prostate cancer, is composed of hormone-dependent columnar secretory epithelial cells and a mixture of hormone-independent cuboidal epithelial cells, basal epithelial cells, and stromal cells. Androgen ablation causes the gland to regress due to the selective loss of the secretory luminal epithelial cells that undergo apoptosis. Most, if not all, of the studies examining the induction of apoptosis and the mechanism of regression have used young adult males at around 3 months of age. Prostate cancer, however, is a disease of older males, and we have therefore investigated whether age-related changes in hormone sensitivity and apoptosis occur in the ventral prostate of aged animals (12 months old) compared to young animals (3 months old). We have observed distinct differences in the morphology of the prostate between young and old rats prior to castration and a significant slowing in the rate of regression after castration in older animals. These changes are accompanied by changes in lipofuscin accumulation and levels of the antioxidant enzymes catalase and manganese (Mn) superoxide dismutase in the gland.
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PMID:Changes in hormone sensitivity in the ventral prostate of aging Sprague-Dawley rats. 1200 36

Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.
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PMID:Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. 1211 87

Little is known about the roles of androgens in the regulation of redox state in the prostate, a cellular process believed to profoundly influence normal and aberrant prostate functions. We demonstrate that castration induced discrete oxidative stress (OS) in the acinar epithelium of rat ventral prostate (VP), as evident from marked increases in 8-hydroxy-2'-deoxy-guanosine and 4-hydroxynonenal protein adducts in the regressing epithelium. Testosterone replacement partially reduced OS in VP epithelia of castrates, but the level remained higher than in intact rats. Quantification of steady-state mRNA levels of 14 genes involved in the anabolism and catabolism of reactive oxygen species (ROS) showed that castration resulted in dramatic increases of three ROS-generating NAD(P)H oxidases (Noxs) including Nox1, gp91(phox), and Nox4, significant reductions of key ROS-detoxifying enzymes (superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5), and unchanged levels of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase. Testosterone replacement in castrated rats partially reduced expression of Noxs but restored expression of superoxide dismutase 2, glutathione peroxidase 1, thioredoxin, and peroxiredoxin 5 to complete normalcy and induced a compensatory increase in expression of catalase, glutathione reductase, gamma-glutamyl transpeptidase, and glutathione synthetase in the regenerating VP. Expression of superoxide dismutase 1, glutathione S-transferase-pi, and glucose-6-phosphate dehydrogenase was unaffected by castration and testosterone replacement. These findings indicate androgen-deprivation induces OS in the rat VP through elevation of ROS anabolism and diminution of antioxidant detoxification. Androgen replacement partially reduces OS in rat VP to precastration levels. Expression of Noxs remained high amid a broad-based recovery of antioxidant defense mechanism(s). These data might have implications on the use of androgen blockade for prostate cancer prevention and androgen therapy for andropause treatment in elderly men.
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PMID:Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. 1463 23

Clinical application of anticancer agents has been often hampered by toxicity against normal cells, so the achievement of their cancer-specific action is still one of the major challenges to be addressed. Previously, we reported that arsenic trioxide (As2O3) could be a promising new drug against not only leukemia but also solid tumors. The cytotoxicity of As2O3 occurred through the generation of reactive oxygen species (ROS), thus inhibiting radical scavenging systems would enhance the therapeutic efficacy of As2O3 provided that normal cells were relatively resistant to such a measure. Here, we report that the combination therapy of As2O3 with L-buthionine-sulfoximine (BSO), which inhibits a critical step in glutathione synthesis, effectively enhanced in vitro growth inhibition effect of As2O3 on all 11 investigated cell lines arising from prostate, breast, lung, colon, cervix, bladder, and kidney cancers, compared with As2O3 treatment alone. Furthermore, this combination enhanced cytotoxicity to cell lines from prostate cancer with less toxicity to those from normal prostate. In vitro cytotoxic assay using ROS-related compounds demonstrated that hydrogen peroxide (H2O2) is a major cytotoxic mediator among ROS molecules. Biochemical analysis showed that combined use of As2O3 and BSO blocked H2O2-scavenging systems including glutathione, catalase, and glutathione peroxidase, and that the degree of this blockade was well correlated with intracellular ROS levels and sensitivity to this treatment. Finally, the effectiveness of the combination therapy of As2O3 with BSO was demonstrated with an orthotopic model of prostate cancer metastasis. We propose that the combination therapy of As2O3 with BSO is a valid means of blockade of H2O2-scavenging system, and that the combination of a ROS-generating agent with an inhibitor of major scavenging systems is effective in terms of both efficacy and selectivity. Furthermore, because the effective doses of both compounds are within clinically achievable range, this report will lead to immediate benefit for the development of a new cancer therapy.
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PMID:Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine. 1500 36

Mutagenic oxidative DNA base damage increases with age in prostatic tissue. Various factors may influence this increase including: increased production of reactive oxygen species, increased susceptibility to oxidative stress, alterations in detoxifying enzyme levels or defects in DNA repair. Using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, we show increased levels of oxidative DNA base lesions, 8-hydroxyguanine (8-oxoG), 8-hydroxyadenine (8-oxoA) and 5-hydroxycytosine (5OHC) over the baseline in PC-3 and DU-145 prostate cancer cells following exposure to ionizing radiation and a repair period. Nuclear extracts from PC-3 and DU-145 prostate cancer cell lines are defective in the incision of 8-oxoG, 5OHC and thymine glycol (TG) relative to the non-malignant prostate cell line. Consistent with reduced expression of OGG1 2a, incision of 8-oxoG is reduced in PC-3 and DU-145 mitochondrial extracts. We also show a correlation between severely defective incision of TG and 5OHC and reduced levels of NTH1 in PC-3 mitochondria. The antioxidant enzymes, glutathione peroxidase (GPx), catalase and superoxide dismutases (SOD1, SOD2), have altered expression patterns in these cancer cell lines. Genetic analysis of the OGG1 gene reveals that both PC-3 and DU-145 cell lines harbor polymorphisms associated with a higher susceptibility to certain cancers. These data suggest that the malignant phenotype in PC-3 and DU-145 cell lines may be associated with defects in base excision repair and alterations in expression of antioxidant enzymes.
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PMID:Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145. 1504 26


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