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)

Freeze-dried black raspberries have been shown to inhibit the development of chemically induced esophageal and colon cancer in rodents. In addition, organic extracts of black raspberries inhibit benzo(a)pyrene (BaP)-induced cell transformation in vitro. The molecular mechanisms through which black raspberries inhibit carcinogenesis remain unclear. We investigated the effects of black raspberry extracts on transactivation of activated protein 1 (AP-1) and nuclear factor kappaB (NFkappaB) induced by BaP diol-epoxide (BPDE), the ultimate carcinogen of BaP, in mouse epidermal JB6 Cl 41 (Cl 41) cells. Black raspberries were extracted with methanol, and the methanol extract was partitioned and chromatographed into several fractions designated RU-F003, RU-F004, RU-DM, and RU-ME. Pretreatment of Cl 41 cells with RU-F003, RU-DM, or RU-ME resulted in an inhibition of BPDE-induced AP-1 and NFkappaB activities. The RU-ME fraction was the most potent inhibitor among the fractions tested. In contrast, fraction RU-F004 did not inhibit BPDE-induced AP-1 or NFkappaB activities in Cl 41 cells. The inhibitory effects of RU-ME on BPDE-induced activation of AP-1 and NFkappaB appear to be mediated via inhibition of mitogen activated protein kinase activation and inhibitory subunit kappaB phosphorylation, respectively. Pretreatment of cells with berry fractions did not result in an inhibition of BPDE binding to DNA; thus, this was not a mechanism of reduced AP-1 and NFkappaB activities. None of the fractions was found to affect p53-dependent transcription activity. In view of the important roles of AP-1 and NFkappaB in tumor promotion/progression, these results suggest that the ability of black raspberries to inhibit tumor development may be mediated by impairing signal transduction pathways leading to activation of AP-1 and NFkappaB. The RU-ME fraction appears to be the major fraction responsible for the inhibitory activity of black raspberries.
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PMID:Inhibition of benzo(a)pyrene diol-epoxide-induced transactivation of activated protein 1 and nuclear factor kappaB by black raspberry extracts. 1246 Aug 99

Uptake, intracellular concentration, localization and photodynamic effects of a haematoporphyrin derivative (HpD, Photosan-3) were compared in human glioma (BMG-1, wild-type p53) and squamous carcinoma (4451, mutated p53) cell lines. Concentration and time dependence of cellular uptake of HpD was assayed from methanol extracts and whole cell suspension spectroscopy, while localization was studied by fluorescence microscopy-based image analysis. Colony-forming ability, apoptosis, cell-cycle progression and cytogenetic damage (micronuclei formation) were investigated as parameters of photodynamic response following irradiation with red light. BMG-1 cells were more sensitive to the photodynamic treatment than 4451 cells, although the 4451 cells accumulated a higher amount of HpD and did not differ significantly from BMG-1 cells with respect to intracellular localization. Photodynamically-induced cytogenetic damage and apoptosis were considerably higher in BMG-1 cells as compared to 4451 cells. The present results strongly suggest that manifestation of the photodynamically-induced lesions in the form of cytogenetic damage and apoptosis are among the important determinants of cellular sensitivity to HpD-PDT besides the photodynamic dose (intracellular concentration of the photosensitizer and the light dose).
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PMID:Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines. 1263 83

Polyozellus multiplex, a Korean wild mushroom, was extracted using methanol, and the extract was further fractionated with water and ethylacetate. Assay of each fraction with MTT revealed significant tumoristatic effects of the water fraction of Polyozellus multiplex against human gastric and other cancer cells but not normal human lymphocytes. Modifying effects of the water fraction on glandular stomach mucosa were investigated in male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The dietary 0.5% or 1% water fraction of Polyozellus multiplex significantly increased glutathione S-transferase (GST) and superoxide dismutase (SOD) activities, and showed a tendency for increase in glutathione (GSH) levels, compared to the MNNG alone group. It also caused a significant reduction in proliferating cell nuclear antigen (PCNA)-labeling index of the glandular stomach epithelium, along with increase in p53 tumor suppressor gene expression. These results suggest that Polyozellus multiplex is a candidate for chemoprevention against gastric cancer.
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PMID:Polyozellus multiplex, a Korean wild mushroom, as a potent chemopreventive agent against stomach cancer. 1456 27

Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.
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PMID:Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line. 1558 81

6-methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid derived from the methanol extracts of Hylomecon hylomeconoides, showed a dose-dependent effect at 1-10 microM on causing apoptotic cell death in HT29 colon carcinoma cells (IC50 = 5.0+/-0.2 microM). Treatment of HT-29 cells with 6ME resulted in the formation of internucleosomal DNA fragmentation. Treatment of the cells with 6ME caused activation of caspase-3, -8 and 9 protease and subsequent proteolytic cleavage of poly(ADP-ribose)polymerase. 6ME increased the expression of p53 and Bax and decreased the expression of Bid. These results indicate that p53 and proapoptotic Bcl-2 family proteins might participate in the antiproliferative activity of 6ME in HT29 cells.
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PMID:Apoptosis inducing effects of 6-methoxydihydrosanguinarine in HT29 colon carcinoma cells. 1564

We recently reported a beta-peptide foldamer, beta53-1, that folds into a 14-helix in aqueous solution, binds the oncoprotein hDM2 with submicromolar affinity, and potently inhibits the interaction of hDM2 with a peptide derived from the activation domain of p53 (p53AD). Here, we present the solution structure of beta53-1 in methanol. Details of the structure illustrate fundamental and novel elements of beta-peptide folding and recognition. These elements include the detailed arrangement of a complex, 14-helix-stabilizing salt bridge on one helical face, and a unique "wedge into cleft" packing interaction along a second. The structure also reveals how a subtle distortion in the beta53-1 14-helix geometry alters the presentation of its recognition epitope, rendering it particularly well suited for alpha-helix mimicry. The solution structure of beta53-1 demonstrates that well folded beta-peptide oligomers can effectively present an extended, highly variable surface that could be used as a general platform for targeting critical protein-protein interfaces.
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PMID:Solution structure of a beta-peptide ligand for hDM2. 1578 63

Caesalpinia sappan L. (C. sappan) has been used in Oriental medicine as an antitumor agent. The present study shows the effects of the chloroform extract of C. sappan on cell death in head and neck cancer cell lines. The viability of HNSCC4 and HNSCC31 cells (head and neck cancer cell lines) was noticeably decreased compared to that of HaCaT cells (control group) in the presence of chloroform extract. No significant difference was observed in the viability of HNSCC4 and HNSCC31 cells when compared with HaCaT cells in the presence of n-butanol, methanol, and water extracts. Exposure to the chloroform extract of C. sappan resulted in an increase in the Sub-G1 phase of the cell cycle and condensation and shrinkage of nuclei in the HNSCC4 and HNSCC31 cells. The levels of p53 and p21WAF1/CIP1 were also increased in the HNSCC4 and HNSCC31 cells. The results suggest that the chloroform extract of C. sappan may increase cell death in the HNSCC4 and HNSCC31 cells, which is linked to increased cellular levels of p53 and p21WAF1/CIP1.
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PMID:Caesalpinia sappan induces cell death by increasing the expression of p53 and p21WAF1/CIP1 in head and neck cancer cells. 1604 58

Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a dose-dependent manner, while it was less toxic to normal human cell lines. Animal experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.
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PMID:Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. 1700 87

Flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine that has long been used in Korea as both a food additive and antitumor agent. It was previous reported that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), inhibited the proliferation and induced apoptosis in human osteosarcoma (HOS) cells. This study examined the mechanisms involved in the RCMF-mediated apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis in HOS cells by inducing p53 in the cells resulting in the decrease in Bcl-2 level, activation of Bax, and cytoplasmic release of cytochrome c, which led to the translocation of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) into the nucleus. However, the RCMF-induced apoptosis was suppressed by transfecting the cells with antisense p53 oligonucleotides but not by treating them with a MAPK or caspase inhibitor. This suppression occurred through the regulation of Bcl-2 members as well as by preventing the nuclear translocation of the mitochondrial apoptogenic factors. Overall, it appears that p53-mediated mitochondrial stress and the nuclear translocation of AIF and EndoG are mainly required for the apoptosis induced by RCMF.
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PMID:Caspase-independent death of human osteosarcoma cells by flavonoids is driven by p53-mediated mitochondrial stress and nuclear translocation of AIF and endonuclease G. 1735 95

The human tumour suppressor P53 is a key protein involved in tumour suppression. P53 acts as a "guardian of genome" by regulating many target genes involved in cell cycle regulation, DNA repair and apoptosis. We report the P53 expression by the methylotrophic yeast Pichia pastoris using the methanol inducible AOX1 promoter. We have produced the rP53 in intracellular form as well as secreted using the Saccharomyces cerevisiae alpha-mating factor prepro-leader sequence in two genetic contexts of Pichia, Mut(s) and Mut(+). The intracellular P53 was successfully produced by Mut(s) (KM71) as well as Mut(+) (X33) strains, however, the secreted form was mainly observed in the Mut(s) strain, despite a higher number of p53 copies integrated in the Mut(+) strain. Interestingly, in Mut(s) phenotype, the medium pH influences markedly the rP53 production since it was higher at pH 7 than 6.
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PMID:High-level expression of human tumour suppressor P53 in the methylotrophic yeast: Pichia pastoris. 1748 79


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