UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ADAM (a disintegrin and metalloprotease) family is a group of transmembrane proteins containing cell adhesive and proteolytic functional domains. Microarray analysis detected elevated ADAM9 during the transition of human LNCaP prostate cancer cells from an androgen-dependent to an androgen-independent and metastatic state. Using a prostate tissue array (N = 200), the levels of ADAM9 protein expression were also elevated in malignant as compared with benign prostate tissues. ADAM9 protein expression was found in 43% of benign glands with light staining and 87% of malignant glands with increasing intensity of staining. We found that ADAM9 mRNA and protein expressions were elevated on exposure of human prostate cancer cells to stress conditions such as cell crowding, hypoxia, and hydrogen peroxide. We uncovered an ADAM9-like protein, which is predominantly induced together with the ADAM9 protein by a brief exposure of prostate cancer cells to hydrogen peroxide. Induction of ADAM9 protein in LNCaP or C4-2 cells can be completely abrogated by the administration of an antioxidant, ebselen, or genetic transfer of a hydrogen peroxide degradative enzyme, catalase, suggesting that reactive oxygen species (ROS) are a common mediator. The induction of ADAM9 by stress can be inhibited by both actinomycin D and cycloheximide through increased gene transcription and protein synthesis. In conclusion, intracellular ROS and/or hydrogen peroxide, generated by cell stress, regulate ADAM9 expression. ADAM9 could be responsible for supporting prostate cancer cell survival and progression. By decreasing ADAM9 expression, we observed apoptotic cell death in prostate cancer cells.
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PMID:Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. 1701 8

Radiation therapy is a standard treatment for prostate cancer (PC). The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS). Adjuvant androgen deprivation (AD) therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR)(+) 22rv1 and AR(-) PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS) levels, resulting in dose-dependent activation of phospho-p38 and pAKT, and increased expression of clusterin, catalase, and manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, and CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, and glutathione reductase. Consequently, AD significantly facilitated the response of AR(+) cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.
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PMID:Androgen induces adaptation to oxidative stress in prostate cancer: implications for treatment with radiation therapy. 1732 45

Guggulsterone, a constituent of Indian Ayurvedic medicinal plant Commiphora mukul, causes apoptosis in cancer cells but the sequence of events leading to cell death is poorly understood. We now show that guggulsterone-induced cell death in human prostate cancer cells is caused by reactive oxygen intermediate (ROI)-dependent activation of c-Jun NH(2)-terminal kinase (JNK). Exposure of PC-3 and LNCaP cells to apoptosis inducing concentrations of guggulsterone resulted in activation of JNK and p38 mitogen-activated protein kinase (p38 MAPK) in both cell lines and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LNCaP cells. The guggulsterone-induced apoptosis in PC-3/LNCaP cells was partially but statistically significantly attenuated by pharmacologic inhibition (SP600125) as well as genetic suppression of JNK activation. On the other hand, pharmacologic inhibition of p38 MAPK activation in PC-3 or LNCaP cells (SB202190) and ERK1/2 activation in LNCaP cells (PD98059) did not protect against guggulsterone-induced cell death. The guggulsterone treatment caused generation of ROI in prostate cancer cells but not in a normal prostate epithelial cell line (PrEC), which was also resistant to guggulsterone-mediated JNK activation. The guggulsterone-induced JNK activation as well as cell death in prostate cancer cells was significantly attenuated by overexpression of catalase and superoxide dismutase. In addition, guggulsterone treatment resulted in a decrease in protein level and promoter activity of androgen receptor in LNCaP cells. In conclusion, the present study reveals that the guggulsterone-induced cell death in human prostate cancer cells is regulated by ROI-dependent activation of JNK and guggulsterone inhibits promoter activity of androgen receptor.
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PMID:Guggulsterone-induced apoptosis in human prostate cancer cells is caused by reactive oxygen intermediate dependent activation of c-Jun NH2-terminal kinase. 1767 Dec 14

The involvement of mitochondrial glycerophosphate dehydrogenase (mGPDH) has previously been established in the production of ROS in prostate cancer cell lines (LNCaP, DU145, PC3 and CL1). The current study demonstrates that the mRNA level of mGPDH in prostate cancer cells is 3.3-8.9-fold higher compared to the normal prostate epithelial cell line, PNT1A. This is consistent with the enzymatic activity and protein level of mGPDH. However, cytochrome c oxidase (COX) activity is 2.9-3.2-fold down-regulated in androgen-independent prostate cancer cell lines. The level of antioxidant enzymes, catalase, MnSOD and CuZnSOD are up-regulated in prostate cancer cell lines. Furthermore, it was observed that the activity of mGPDH is significantly higher in liver tissues from all mice with cancer compared to liver tissues from control mice. These data suggest that the up-regulation of mGPDH, due to a highly glycolytic environment, contributes to the overall increase in ROS generation and may result in the progression of the cancer.
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PMID:Increased expression of mitochondrial glycerophosphate dehydrogenase and antioxidant enzymes in prostate cancer cell lines/cancer. 1788 33

Overexpression of the tumor suppressor gene, wild-type p53 (wtp53), using adenoviral vectors (Adp53) has been suggested to kill cancer cells by hydroperoxide-mediated oxidative stress [1,2] and nutrient distress induced by the glucose analog, 2-deoxyglucose (2DG), has been suggested to enhance tumor cell killing by agents that induce oxidative stress via disrupting hydroperoxide metabolism [3,4]. In the current study clonogenic cell killing of PC-3 and DU-145 human prostate cancer cells (lacking functional p53) mediated by 4 h exposure to 50 plaque forming units (pfus)/cell of Adp53 (that caused the enforced overexpression of wtp53) was significantly enhanced by treatment with 2DG. Accumulation of glutathione disulfide was found to be significantly greater in both cell lines treated with 2DG+Adp53 and both cell lines treated with 2DG+Adp53 showed a approximately 2-fold increases in dihydroethidine (DHE) and 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CDCFH(2)) oxidation, indicative of increased steady-state levels of O(2)(.-) and hydroperoxides, respectively. Finally, overexpression of catalase or glutathione peroxidase using adenoviral vectors partially, but significantly, protected DU-145 cells from the toxicity induced by 2DG+Adp53 treatment. These results show that treatment of human prostate cancer cells with the combination of 2DG (a nutrient stress) and overexpression of the tumor suppressor gene, wtp53, enhances clonogenic cell killing by a mechanism that involves oxidative stress as well as allowing for the speculation that inhibitors of glucose and hydroperoxide metabolism can be used in combination with Adp53 gene therapy to enhance therapeutic responses.
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PMID:2-Deoxyglucose combined with wild-type p53 overexpression enhances cytotoxicity in human prostate cancer cells via oxidative stress. 1815 76

Molecular mechanisms for the gamma-ionizing radiation (IR) resistance of human prostate cancer cells, PC-3, are not quite clear. Since the low-LET-IR effects are primarily manifested by the generation of reactive oxygen species (ROS), the IR-induced expressions both of ROS-metabolizing antioxidant enzymes, such as Mn- and CuZn superoxide dismutases (SODs) and catalase (Cat), and of the transcriptional nuclear factor-kappaB (NF-kappaB) were explored. A substantial increase in the concentrations of SODs was observed in the cells irradiated by 10 and 20 Gy relative to those irradiated by 0 and 2 Gy, while the Cat and NF-kappaB expressions were found to be fairly stable. A system biology model was developed to shed more light on how MnSOD affects the biological state of cells depending upon the production of H(2)O(2). By raising the initial presence of MnSOD in the 0.7-10 microM concentration range, the time-dependent concentrations of H(2)O(2) for various initial levels of MnSOD were contrasted. The radioresistance of PC-3 cells is suggested to be associated with the positive, feed-forward vicious circle established between the H(2)O(2)-mediated elevation of MnSOD expression.
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PMID:Experimental and systems biology studies of the molecular basis for the radioresistance of prostate carcinoma cells. 1826 64

Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2'-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O(2)(-)) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2'-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O(2)(-) radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed.
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PMID:Angiotensin II induces oxidative stress in prostate cancer. 1831 86

Apigenin, a plant flavone, potentially activates wild-type p53 and induces apoptosis in cancer cells. We conducted detailed studies to understand its mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin resulted in the stabilization of p53 by phosphorylation on critical serine sites, p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65 transcriptional activity, and induction of p21/WAF-1 in a dose- and time-dependent manner. Apigenin at these doses resulted in ROS generation, which was accompanied by rapid glutathione depletion, disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, and apoptosis. Interestingly, we observed accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment. All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine, p53 inhibitor pifithrin-alpha, and enzyme catalase. Apigenin-mediated p53 activation and apoptosis were further attenuated by p53 antisense oligonucleotide treatment. Exposure of cells to apigenin led to a decrease in the levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation. Treatment with the caspase inhibitors Z-VAD-FMK and DEVD-CHO partially rescued these cells from apigenin-induced apoptosis. In vivo, apigenin administration demonstrated p53-mediated induction of apoptosis in 22Rv1 tumors. These results indicate that apigenin-induced apoptosis in 22Rv1 cells is initiated by a ROS-dependent disruption of the mitochondrial membrane potential through transcriptional-dependent and -independent p53 pathways.
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PMID:Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation. 1834 37

Green tea and black tea (BT) contain gallated [(-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate] and nongallated [(-)-epicatechin, (-)-epigallocatechin (EGC)] tea polyphenols (PP). During BT production, PP undergo oxidation and form larger polymers such as theaflavins (THE) and thearubigins, which contribute to the health benefit of BT. This article gives an overview of the role of chemical characteristics and endogenous metabolism of tea PP and their bioavailability in humans and describes attempts to increase their bioavailability. At pH close to neutral, EGCG and EGC form homo- and heterodimers generating hydrogen peroxide. To confirm the pH instability of EGCG, EGC, and THE in cell culture medium, their antiproliferative activity was determined in the presence and absence of catalase. The antiproliferative activity in LNCaP prostate cancer cells was decreased when incubated with catalase prior to EGCG, EGC, and THE treatment. In addition, new findings demonstrated that the formation of methyl-EGC increased the stability at neutral pH compared with EGC. Approaches to increase the bioavailability of flavan-3-ols are reviewed, which include the administration of tea in combination with fruit juices, coadministration with piperine, and peracetylation of EGCG. Future intervention studies will need to focus on the bioactivity not only of green tea and BT PP but also of their metabolites and biotransformation products.
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PMID:Nongallated compared with gallated flavan-3-ols in green and black tea are more bioavailable. 1864 Dec 2

A number of epidemiological studies suggest that the consumption of green tea reduces the incidence of prostate cancer. As the major catechins present in green tea are potent antioxidants, we hypothesized that genetic and cellular damage induced by oxygen free radicals could be significantly reduced by potent antioxidants in green tea, thus reducing the cumulative genetic and cellular damage with age, and slowing or preventing tumour formation. Long-term administration of a decaffeinated green tea extract to Lobund-Wistar rats for periods up to 26 months almost halved the incidence of primary tumours in the genitourinary tract when compared with an age-matched cohort receiving just water. We observed no inhibition of DNA adduct formation or lipid peroxidation in animals consuming green tea compared with animals consuming deionized water. The decrease in tumour formation was associated with an increase in 8-hydroxy-2'deoxyguanosine and 4-hydroxynonenal content (markers of DNA adduct formation and lipid peroxidation, respectively) in the epithelium of the ventral prostate in aging animals. In addition, there was an increase in 8-hydroxy-2'deoxyguanosine expression, but no change in 4-hydroxynonenal expression in the seminal vesicles of older animals. An age-associated increase in expression of the antioxidant enzymes manganese superoxide dismutase and catalase in the epithelium of the ventral prostate of aging animals was observed. Furthermore, there was also an increase in manganese superoxide dismutase expression, but no change in catalase expression in the seminal vesicles of older animals. These data demonstrate that consumption of green tea decreases the incidence of genitourinary tract tumours in the Lobund-Wistar rat, but has no effect on age-associated DNA adduct formation and lipid peroxidation in the ventral prostate and seminal vesicles of the aging rat.
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PMID:The effect of green tea on oxidative damage and tumour formation in Lobund-Wistar rats. 1894 71

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