Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we investigated the protective mechanism of quercetin (QUE) and its glycosides, rutin (RUT) and quercitrin (QUI), on reactive oxygen species (ROS)-dependent (H(2)O(2)) and -independent (chemical anoxia) cell death in rat glioma C6 cells. Induction of HO-1 protein expression was detected in QUE- but not RUT- or QUI-treated C6 cells, and this was prevented by cycloheximide and actinomycin D. Incubation of C6 cells with QUE, but not RUT or QUI, protected C6 cells from H(2)O(2)- and chemical anoxia-induced cytotoxicity according to the MTT and LDH release assays. Apoptotic characteristics including chromatin condensation, DNA ladders, and hypodiploid cells appeared in H(2)O(2)-and chemical anoxia-treated C6 cells, and those events were significantly suppressed by adding QUE (but not RUT or QUI). Increases in caspase 3, 8, and 9 enzyme activities with decreases in pro-PARP and pro-caspase 3 protein levels and an increase in cleaved D4-GDI protein were identified in H(2)O(2)-and chemical anoxia-treated C6 cells, and these were blocked by the addition of QUE, but not by RUT or QUI. Intracellular peroxide levels increased with H(2)O(2) and decreased with chemical anoxia, and the addition of QUE reduced the intracellular peroxide levels induced by H(2)O(2). Results of an anti-DPPH radical assay showed that QUE, RUT, and QUI dose-dependently inhibited the production of DPPH radicals in vitro; however, QUE (but not RUT or QUI) prevention of DNA damage induced by OH radicals was identified with a plasmid digestion assay. Increases in phosphorylated ERK and p53 protein expressions were detected in H(2)O(2)- but not chemical anoxia-treated C6 cells, and the addition of QUE significantly blocked H(2)O(2)-induced phosphorylated ERK and p53 protein expressions. Adding the HO-1 inhibitors, SnPP, CoPP, and ZnPP, reversed the protective effect of QUE against H(2)O(2)- and chemical anoxia-induced cell death according to the MTT assay and morphological observations. Additionally, QUE exhibited inhibitory effects on LPS/TPA-induced transformation in accordance with a decrease in MMP-9 enzyme activity and iNOS protein expression in C6 cells. Taken together, the results of this study suggest that QUE exhibits an inhibitory effect on both ROS-dependent and -independent cell death, and induction of HO-1 protein expression is involved.
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PMID:Quercetin inhibition of ROS-dependent and -independent apoptosis in rat glioma C6 cells. 1664 78

Tumor markers play an important role in the diagnosis of cancer. Cervical carcinoma and endometrial cancer are the most frequent diseases of the reproductive organs and their morbidity rates are constantly increasing. Many tumor markers may be used in the diagnosis and monitoring of endometrial and cervical carcinoma, for example CA 125, SCC-Ag, TPA, TPS, and CYFRA 21-1. New tumor markers useful in the early diagnosis and in monitoring the treatment and recurrence of the uterine cancer are still being sought. Investigations are underway on such substances as cytokines (e.g. M-CSF) and molecular markers of carcinogenesis (e.g. K-ras and p53).
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PMID:[Tumor markers useful in the diagnostics and monitoring of endometrial and cervical cancer]. 1736 80

Interphase fluorescent in situ hybridization on unstimulated peripheral blood mononuclear cells (I-FISH-PBMC) is used to detect chromosomal abnormalities such as 11q-, 13q-, 17p-, and trisomy 12 in chronic lymphocytic leukemia (CLL). A total of 56 samples from 49 patients with CLL were studied using commercially available probes for chromosome regions 11q22.3 (ATM), 13q14 (13S272), 17p13 (p53) and 12 centromere (D12Z3). We compared the results obtained with I-FISH-PBMC and those with I-FISH on TPA (tetradecanoylphorbol acetate; phorbol-12-myristate-13-acetate) stimulated peripheral blood cells (I-FISH-TPA) used for conventional cytogenetics, to evaluate the usefulness of I-FISH-TPA. The proportion of abnormal nuclei obtained with the I-FISH-TPA was higher than that found with I-FISH-PBMC (P < 0.001). Consequently, 15 cases with a negative or borderline result with I-FISH-PBMC became positive with I-FISH-TPA for 11q- (n = 2), 13q- (n = 9), and trisomy 12 (n = 4). In all but one of these, chromosomal abnormalities were confirmed by either metaphase FISH or conventional G-banding. Detection of cytogenetic aberrations thus increased from 51% with I-FISH-PBMC to 78% with I-FISH-TPA. Notably, all 15 of the cases that reached the diagnostic thresholds for 11q-, 13q-, and trisomy 12 had a slight lymphocytosis. An absolute lymphocyte count <8.7 x 10(9)/L was found to be the critical threshold (P = 0.037) below which I-FISH-TPA rather than I-FISH-PBMC should be performed. Not only could I-FISH-TPA detect a higher proportion of abnormal interphase nuclei, but it could also identify abnormal CLL cases that might be overlooked with use of I-FISH-PBMC, especially those with low absolute lymphocyte counts. I-FISH-TPA is thus a reliable technique for clinical diagnostics in CLL.
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PMID:Detection of chromosomal abnormalities in chronic lymphocytic leukemia increased by interphase fluorescence in situ hybridization in tetradecanoylphorbol acetate-stimulated peripheral blood cells. 1749 59

Three new triterpene oligoglycosides, okhotosides B 1 ( 1), B 2 ( 2), and B 3 ( 3), have been isolated from the sea cucumber Cucumaria okhotensis along with the known compounds frondoside A ( 4), frondoside A 1, cucumarioside A 2-5, and koreoside A. The structures of 1- 3 were elucidated on the basis of their spectroscopic data (2D NMR and MS). Compounds 1- 3 were moderately toxic against HeLa tumor cells. Frondoside A ( 4) showed more potent cytotoxicity against THP-1 and HeLa tumor cell lines (with IC 50 values of 4.5 and 2.1 microg/mL, respectively) and decreased both the AP-1-dependent trascriptional activities induced by UVB, EGF, or TPA in JB6-LucAP-1 cells and the EGF-induced NF-kappaB-dependent transcriptional activity in JB6-LucNF-kB cells at doses of about 1 microg/mL. At the same doses, it increased the p53-dependent transcriptional activity in nonactivated JB6-Lucp53 cells and inhibited the colony formation of JB6 P (+) Cl 41 cells activated with EGF (INCC 50 = 0.8 microg/mL).
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PMID:Constituents of the sea cucumber Cucumaria okhotensis. Structures of okhotosides B1-B3 and cytotoxic activities of some glycosides from this species. 1828 10

The tumor suppressor p53 can translocate into mitochondria and activate apoptosis. Here we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by blocking mitochondrial permeability transition pore using cyclosporine A (CsA) and bongkrekic acid (BA) in skin epidermal JB6 cells and skin tissues. Our results demonstrated that CsA and BA blocked TPA-induced p53 translocation, leading to protection against the loss of mitochondrial membrane potential and Complex I activity, and eventually suppression of apoptosis. Thus, our results suggest that mitochondrial permeability transition is required for p53 mitochondrial translocation.
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PMID:Blocking mitochondrial permeability transition prevents p53 mitochondrial translocation during skin tumor promotion. 1835 38

Cervical carcinoma is the most frequent disease of the female reproductive organs. The tumour markers may be helpful: in early diagnosis of cervical cancer, the initial assesment of the extent of the disease, monitoring of tumour growth or tumour volume reduction, recurrence of cancer, and have been used for monitoring of the clinical course of chemotherapy and radiotherapy. In this paper we have focused on the role of new tumour markers, especially cytokines (for example G-CSF, VEGF) and molecular markers of carcinogenesis (for example Bcl-2 and p53), in comparison to typical tumour markers useful in diagnostic of cervical cancer such as CA 125, SCC-Ag, TPA, TPS, CYFRA 21-1.
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PMID:[New tumour markers useful in diagnostics and monitoring of cervical cancer]. 1859 8

Finding and development of new bladder cancer markers is still a very dynamic field. Because of the mass of all these markers it is impossible to report all of them. This paper reviews the role of bladder cancer markers in diagnosis and highlights the most important biomarkers studied and reported recently. A medline based literature search was performed to examine the field of bladder cancer markers. Major topics focus on selected bladder cancer markers from nearly all categories of the wide field of bladder cancer markers: Hematuria, FISH, FGFR3, SURVIVIN, u-PAR, TP53 mutation, HER-2/neu, TPA, NMP22, CK-19, CK-20, CYFRA 21-1. The use and clinical importance as diagnostic help are discussed. In this review a highlight to some of the most important markers was made. Further determination of recurrence and progression marker will contribute to establish better treatments for the individual patient. Molecular staging of urological tumors will allow selecting cases that will require systemic treatment. It is necessary and important to integrate under the same objectives basic and clinical research.
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PMID:Focus on urinary bladder cancer markers: a review. 1892 60

The Tg.AC mouse model was used to assess the utility of a short-term screening assay to evaluate compounds with suspected carcinogenic/anticarcinogenic activity. Crude broccoli juice (BROC) was evaluated for antitumorigenic effects against 12-Otetradecanoylphorbol-13-acetate (TPA) and benzo[a]pyrene (B[a]P)-induced tumors. Groups of female mice were dosed three times a week (200 muL/mouse) with one of the following: acetone vehicle control, TPA (2.5 mug/mouse), B[a]P (250 mug/mouse), BROC/TPA, or BROC/B[a]P. BROC (200 muL, 1:1 acetone) was dermally administered 1 h prior to the administration of either TPA or B[a]P to evaluate anticarcinogenic activity. Papilloma numbers were recorded weekly for each mouse. Following 13 weeks of treatment, samples from the dermal test site from all mice were examined histologically. B[a]P-induced tumors were evaluated for transgene expression by RT-PCR and immunohistochemically for cyclin D1 and p53 proteins. TPA and B[a]P induced tumors in all surviving mice. BROC showed effective antitumorigenic activity against TPA but not B[a]P. Tumor development was distinct between TPA (small, benign papillomas) and B[a]P (large, ulcerated, squamous cell carcinomas). The transgene v-Ha-ras, cyclin D1, and p53 proteins were highly expressed in B[a]P tumors where progression to malignancy was rapid (< 13 weeks). The effects induced by B[a]P appeared to cooperate with transgene expression to enhance conversion to malignancy and could serve as a phenotypic indicator for genotoxic versus nongenotoxic carcinogens. The model distinguished differences in tumor response for carcinogenic and anticarcinogenic agents. The Tg.AC mouse model offers a potentially useful screen for identifying new anticarcinogenic agents and directing future mechanistic evaluations.
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PMID:The Tg.AC Transgenic Mouse as a Screening Tool for Anticarcinogens: Broccoli Juice Protected Against 12-O-Tetradecanoylphorbol-13-Acetate (TPA) But Not Benzo[a]Pyrene (B[a]P)-Induced Skin Tumors. 2002 Oct 45

The present study was designed to investigate the protective efficacy of eugenol against skin cancer and probe into the mechanistic aspects. Skin tumors were initiated by applying 160 nmol DMBA and promoted by twice weekly applications of 8.5 nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However, in mice pretreated with 30 microL eugenol, no tumors were detected until 8 wk (following anti-initiation protocol) and until 14 wk (following antipromotion protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors revealed eugenol to ameliorate cell proliferation and elevate apoptosis respectively. The effect of eugenol was assessed on specific stages of carcinogenesis. Initiation with DMBA led to a significant upregulation of p53 expression with a concomitant increase in p21(WAF1) levels in epidermal cells indicating induction of damage to the DNA. However, pretreatment with eugenol led to overexpression of these genes, which probably helped stimulate apoptosis of the initiated cells. To ascertain the molecular mechanisms implicated in the antitumor promoting activity of eugenol, its effect was investigated on markers of tumor promotion and inflammation: ODC activity and iNOS and COX-2 expression, and on levels of proinflammatory cytokines (IL-6, TNF-alpha, and PGE(2)). Eugenol markedly inhibited all. Eugenol also inhibited the upstream signaling molecule: NF-kappaB, which regulates the expression of these genes. TPA-induced depletion of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol. From these results, it could be concluded that eugenol markedly protects against chemically induced skin cancer and acts possibly by virtue of its antiproliferative, anti-inflammatory, and antioxidant activities.
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PMID:Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis. 2004 98

In the present study, we show that the treatment of Epstein-Barr virus (EBV) latently infected Raji cells with TPA/SB caused the cell growth arrest. The Zta-positive cells were predominantly enriched in G0/G1 phase of cell cycle. When Zta expression reached a maximal level, a fraction of Zta expressing cell population reentered S phase. Analysis of the expression pattern of a key set of cell cycle regulators revealed that the expression of Zta and Rta substantially interfered with the cell cycle regulatory machinery in Raji cells, strongly inhibiting the expression of Rb and p53 and inducing the expression of E2F1. Down-regulation of Rb was further demonstrated to be mediated by proteasomal degradation, and p53 and p21 affected at transcription level. The data indicate that both Zta and Rta promote entry into S phase of Raji cells. The important roles of Zta and Rta in EBV lytic reactivation were also demonstrated. Our finding suggests that these two transcriptional activators may act synergistically to govern the expression of downstream early and late genes as well as cellular genes and initiation of lytic cycle and manipulation of cell cycle regulatory mechanisms require the joint and interactive contributions of Rta and Zta.
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PMID:Transactivators Zta and Rta of Epstein-Barr virus promote G0/G1 to S transition in Raji cells: a novel relationship between lytic virus and cell cycle. 2033 40


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