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)

Immunohistochemical verification of the expression of pro-apoptotic protein p53 and anti-apoptotic protein mcl-1 in non-lymphoid structures of human thymus of different age groups has been carried out. It has been shown, that thymic involution starts very early in postnatal ontogenesis, which is testified by the decrease of mcl-1 expression during first months of child life, and at the same time the expression of pro-apoptotic protein p53 noticeably increases during the first year. It was established that deceleration of thymic involution is connected with the decrease of p53 expression, but not with the increase of mcl-1 expression during aging.
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PMID:[Expression of key regulatory apoptotic proteins and their role in thymic involution in human aging]. 1715 17

The effects of the gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, on the cell viability, cell cycle and induction of apoptosis were investigated in human colon cancer colo 205 cells. Gyp was cytotoxic to colo 205 cells with an IC50 of 113.5 microg/ml. The decreasing number of viable cells appeared to be due to the induction of cell cycle arrest and apoptotic cell death, since Gyp induced morphological changes and internucleosomal DNA fragmentation and increased the sub-G1 group. The production of reactive oxygen species and Ca2+ and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment with various concentrations of Gyp. Gyp treatment also gradually decreased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but increased the expression of the pro-apoptotic protein Bax. Gyp increased the levels of p53 and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human colon cancer cells.
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PMID:Gypenosides induced apoptosis in human colon cancer cells through the mitochondria-dependent pathways and activation of caspase-3. 1720 Nov 50

Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhiza Roxb (Zingiberaceae). Xanthorrhizol was tested for a variety of important pharmacological activities including antioxidant and anti-inflammatory activities. An antiproliferation assay using the MTT method indicated that xanthorrhizol inhibited the proliferation of the human breast cancer cell line, MCF-7, with an EC50 value of 1.71 microg/ml. Three parameters including annexin-V binding assay, Hoechst 33258 staining and accumulation of sub-G1 population in DNA histogram confirmed the apoptosis induction in response to xanthorrhizol treatment. Western-blotting revealed down-regulation of the anti-apoptotic bcl-2 protein expression. However, xanthorrhizol did not affect the expression of the pro-apoptotic protein, bax, at a concentration of 1 microg/ml, 2.5 microg/ml and 5 microg/ml. The level of p53 was greatly increased, whilst PARP-1 was cleaved to 85 kDa subunits, following the treatment with xanthorrhizol at a dose-dependent manner. These results, thereby, suggest that xanthorrhizol has antiproliferative effects on MCF-7 cells by inducing apoptosis through the modulation of bcl-2, p53 and PARP-1 protein levels.
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PMID:Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells via apoptosis induction. 1720 Nov 74

The development of radio-resistant tumor cells might be overcome by the use of tumor selective cytotoxic agents in combination with radiation treatment of cancer. Thus, we are exploring the radiomodifying potential of D7, a tumor-inhibitory compound derived from a plant product, diospyrin, in breast carcinoma cells, MCF-7. The present study indicated that D7 could enhance the radiation-induced cytotoxicity and apoptosis through down-regulation of the anti-apoptotic Bcl-2 and COX-2 gene expression, and up-regulation of pro-apoptotic genes, like p53 and p21. The higher expression of PUMA, a pro-apoptotic protein was also observed in the combination treatment. Effect of D7 on up-regulation of p21 expression in irradiated MCF-7 cells was concomitant with the cell cycle arrest in the G1 phase. Thus, it was concluded that D7 could sensitize the effect of radiation in breast carcinoma by regulating the gene expression involved in cell cycle and apoptosis.
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PMID:Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line. 1753 96

Triptolide, derived from the traditional Chinese herb, Tripterygium wilfordii, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous malignancy, has a very poor prognosis and lacks effective therapeutic inventions. We, therefore, investigated the effects of different concentrations of, and different periods of exposure to, triptolide on cell proliferation and apoptosis in the glioma cell lines, U251MG and U87MG, and in normal human fetal astrocytes. Cell proliferation was investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and growth curve analysis, and apoptosis was assessed from genomic DNA fragmentation. Triptolide showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of the pro-apoptotic protein, Bax, to the anti-apoptotic protein, Bcl-2. Since U87MG has the wild-type p53 gene whereas U251MG harbours a mutated p53 gene, our results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. The dose-dependent inhibition of cell proliferation and induction of apoptosis by triptolide may involve upregulation of Bax and downregulation of Bcl-2.
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PMID:The effect of triptolide on apoptosis of glioblastoma multiforme (GBM) cells. 1790 Apr 3

ASPP (apoptosis-stimulating protein of p53) 2 is a pro-apoptotic protein that stimulates the p53-mediated apoptotic response. Here, we provide an overview of the structure and protein-protein interactions of ASPP2. The C-terminus of ASPP2 contains Ank (ankyrin) repeats and an SH3 domain (Src homology 3 domain). The Ank-SH3 domains mediate interactions between ASPP2 and numerous proteins involved in apoptosis such as p53 and Bcl-2. The proline-rich domain of ASPP2 is unfolded in its native state, but was not shown to mediate intermolecular interactions. Instead, it makes an intramolecular domain-domain interaction with the Ank-SH3 C-terminal domains of ASPP2. This intramolecular interaction between the unstructured proline-rich domain and the structured Ank-SH3 domains in ASPP2, which is possible due to the unfolded nature of the proline-rich domain, is proposed to have an important role in regulating the intermolecular interactions of ASPP2 with its partner proteins.
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PMID:Insights into the structure and protein-protein interactions of the pro-apoptotic protein ASPP2. 1795 56

The stilbene resveratrol (RV) initiates p53-dependent apoptosis via plasma membrane integrin alphaVbeta3 in human cancer cells. A thyroid hormone (L-thyroxine, T(4)) membrane receptor also exists on alphaVbeta3. Stilbene and T(4) signals are both transduced by extracellular-regulated kinases 1 and 2 (ERK1/2); however, T(4) promotes cell proliferation in cancer cells, whereas RV is pro-apoptotic. Thyroid hormone has been shown to interfere with RV-induced apoptosis. However, the mechanisms involved are not fully understood. In this study, we examined the mechanism whereby T(4) inhibits RV-induced apoptosis in glioma cells. RV activated conventional protein kinase C and ERK1/2 and caused nuclear localization of cyclooxygenase-2 (COX-2), consequent p53 phosphorylation and apoptosis. RV-induced ERK1/2 activation is involved in not only COX-2 expression but also nuclear COX-2 accumulation. NS-398, a COX-2 inhibitor, did not affect ERK1/2 activation, but reduced the nuclear abundance of COX-2 protein and the formation of complexes of nuclear COX-2 and activated ERK1/2 that are required for p53-dependent apoptosis in RV-treated cells. T(4) inhibited RV-induced nuclear COX-2 and cytosolic pro-apoptotic protein, BcLx-s, accumulation. Furthermore, T(4) inhibited RV-induced apoptosis by interfering with the interaction of nuclear COX-2 and ERK1/2. This effect of T(4) was prevented by tetraiodothyroacetic acid (tetrac), an inhibitor of the binding of thyroid hormone to its integrin receptor. Tetrac did not, in the absence of T(4), affect induction of apoptosis by RV. Thus, the receptor sites on alphaVbeta3 for RV and thyroid hormone are discrete and activate ERK1/2-dependent downstream effects on apoptosis that are distinctive.
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PMID:Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated. 1798 13

We have shown previously that wild-type p53 renders H460 human lung cancer cells more sensitive to apoptosis induction by environmental carcinogen benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), but the mechanism of cell death is not fully understood. The present study provides insights into the mechanism by which BPDE causes apoptosis in H460 cells. Exposure of H460 cells to BPDE resulted in a concentration-dependent apoptotic cell death characterized by cleavage of poly(ADP-ribose)polymerase, DNA condensation, and apoptotic histone-associated DNA fragments released into the cytosol. The BPDE-mediated release of apoptotic histone-associated DNA fragments into the cytosol was also observed in a normal bronchial epithelial cell line BEAS-2B. The BPDE-induced apoptosis in H460 cells correlated with up-regulation of pro-apoptotic protein Bak, downregulation of anti-apoptotic Bcl-2 family members Bcl-2 and Bcl-xL, release of cytochrome c from mitochondria to the cytosol without a change in mitochondrial membrane potential or mitochondrial morphology (electron microscopy), and cleavage of caspase-8, -9, and -3. Ectopic expression of Bcl-2 failed to confer significant protection against BPDE-induced apoptosis in H460 cells. The SV40 immortalized mouse embryonic fibroblasts (MEFs) derived from Bak and Bax double knockout mice, but not Bid knockout mice, were significantly more resistant to BPDE-induced apoptosis compared with the MEFs derived from wild-type mice. The BPDE-induced apoptosis was partially but statistically significantly attenuated in the presence of specific inhibitors of caspase-9 (z-LEHDfmk) and caspase-8 (z-IETDfmk). In conclusion, the present study reveals that BPDE-induced apoptosis in H460 cells is associated with Bak induction and caspase activation but independent of Bcl-2.
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PMID:Benzo[a]pyrene-7,8-diol-9,10-epoxide causes caspase-mediated apoptosis in H460 human lung cancer cell line. 1798 67

Senescent cells are known to be resistant to apoptosis induced by genotoxic stress. Here we examine apoptosis in human diploid fibroblasts that are old but not yet senescent. We found that as cells aged, they became progressively more resistant to UV-induced apoptosis with an eventual apoptosis reduction of 10-20-fold. This behavior tracked a progressive disruption of the normal balance between pro- and anti-apoptotic proteins. In young cells, the level of anti-apoptotic protein BCL-xL quickly fell after UV irradiation while pro-apoptotic protein BAX rose. The increase in BAX tracked the level of P53, a transcriptional regulator of BAX. In older cells, the scenario was quite different. Instead of decreasing, the level of BCL-xL increased dramatically after UV stress so that the ratio of pro-apoptotic BAX to anti-apoptotic BCL-xL remained low. RNAi against BCL-xL restored the UV-sensitivity of old cells, indicating that BCL-xL is itself responsible for the pre-senescence decline in the ability of a genotoxic stress to induce apoptosis.
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PMID:Progressive apoptosis resistance prior to senescence and control by the anti-apoptotic protein BCL-xL. 1826 22

In post-mitotic neurons, the mechanisms of the apoptotic checkpoint that is activated by DNA damage remain unclear. Here we show that in cultured cortical neurons, the DNA damaging agent camptothecin (CPT) reduced transcription of rRNA and disrupted nucleolar staining for B23/nucleophosmin suggesting DNA damage-induced nucleolar stress. Although CPT activated the pro-apoptotic protein p53, the CPT-induced nucleolar stress was unaffected by p53 inhibition. In addition, brain-derived neurotrophic factor-mediated protection from CPT-induced apoptosis prevented neither nucleolar stress nor p53 activation. Therefore, inhibition of rRNA transcription might be upstream of the pro-apoptotic p53 activity. Indeed, short hairpin RNA-mediated inhibition of a RNA-Polymerase-I co-factor, transcription initiation factor IA, attenuated rRNA transcription causing nucleolar stress and p53-dependent neuronal apoptosis. The protein synthesis inhibitor cycloheximide blocked apoptosis that was induced by over-expressed shTIF-IA or active form of p53. Also, the general transcription inhibitor actinomycin D triggered nucleolar stress and activated p53. However, it did not induce apoptosis except at the low concentration of 0.05 microg/mL with stronger inhibitory activity against nucleolar than extranucleolar transcription. Hence, nucleolar stress-activated apoptosis requires extranucleolar transcription. This study identifies the nucleoli of post-mitotic neurons as sensors of DNA damage coupling reduced rRNA transcription to p53-mediated apoptosis that requires de novo expression of protein-coding genes. Thus, rDNA selectivity of DNA damage may determine its ability to induce neuronal apoptosis.
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PMID:Inhibition of nucleolar transcription as a trigger for neuronal apoptosis. 1831 59


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