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)

Chemoprevention is a promising approach to control human cancer. Resveratrol has been shown to have a potent chemopreventive effect in multiple carcinogenesis models. However, the precise mechanism explaining its anti-carcinogenic effect is not clear. This review summarizes recent studies from our laboratory on the mechanisms of resveratrol's effects. In JB6 cells, resveratrol was found to induce apoptosis and inhibit tumor promoter-induced cell transformation. We also found that resveratrol-induced activation of p53 and resveratrol-induced apoptosis occurred through a p53-dependent pathway. The MAP kinases, ERKs, JNKs, or p38 kinases, are involved in resveratrol-induced activation of p53 and apoptosis.
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PMID:Molecular mechanism of the chemopreventive effect of resveratrol. 1262 12

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in large quantities, most notably in grapes and red wine, which has been shown to have anti-inflammatory, chemopreventive and anti-angiogenic effects. We examined whether resveratrol has any effect on growth and gene expression in the human ovarian cancer PA-1 cells. We show that resveratrol inhibits cell growth and induces apoptosis in PA-1 human ovarian cancer cells. We also investigated the effect of resveratrol on changes of global gene expression during resveratrol-induced growth inhibition and apoptosis in PA-1 cells using a human cDNA microarray with 7,448 sequence-verified clones. Out of the 7,448 genes screened, 118 genes were founded to be affected in their expression levels by more than 2-fold after 24-h treatment with 50 micro M resveratrol. Resveratrol treatment of PA-1 cells at the final concentration of 50 micro M for 6, 12, 24 and 48 h and gene expression patterns were analyzed by microarray. Clustering of the genes modulated more than 2-fold at three of the above times points divided the genes into 2 groups. Within these groups, there were specific subgroups of genes whose expressions were substantially changed at the specified time points. One of the most highly up-regulated genes found in this study was NAD(P)H quinone oxidoreductase 1(NQO-1), which has recently been shown to be involved in p53 regulation. Although the precise roles of genes whose expression levels were found to fluctuate after resveratrol treatment remain to be elucidated, we hope that the new view of gene expression in human ovarian cancer cells following resveratrol exposure, as offered by this study, provides clues for the mechanism of resveratrol action.
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PMID:Genome-scale analysis of resveratrol-induced gene expression profile in human ovarian cancer cells using a cDNA microarray. 1263 63

Resveratrol (RV), a polyphenolic stilbene derivative, has been proposed to exert a plethora of beneficial cardiovascular effects. Of these, in particular, inhibition of vascular smooth muscle cell (VSMC) proliferation shows great promise for preventing cardiovascular disease. In the present study, we show that RV leads to a reversible arrest in early S phase of the VSMC cycle, accompanied by an accumulation of hyperphosphorylated retinoblastoma protein. In contrast to studies with other cell systems, RV decreases cellular levels of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip1). This is of particular interest because phosphorylated p53 protein (serine(15)) is strongly enhanced by this substance. We further found that RV only slightly inhibits phosphorylation of Erk 1/2, protein kinase B/Akt, and p70(S6) kinase upon serum stimulation. Thus, inhibition of these kinases is not likely to contribute to the cell cycle effect of RV. Importantly, the observed S phase arrest is not linked to an increase in apoptotic cell death: there was no detectable increase in apoptotic nuclei and in levels of the proapoptotic protein Bax. This is the first study elucidating the molecular pathways mediating the antiproliferative properties of RV in VSMCs.
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PMID:Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. 1264 94

Resveratrol, a constituent of grapes and other foods, has been reported to be a potential cancer chemopreventive agent. Our previous study showed that the antitumor activity of resveratrol occurs through mitogen-activated protein kinases-mediated p53 activation and induction of apoptosis. To develop more effective agents with fewer side effects for the chemoprevention of cancer, we investigated the effect of resveratrol and its structurally related derivatives on epidermal growth factor (EGF)-induced cell transformation. Our results provided the first evidence that one of the resveratrol derivatives exerted a more potent inhibitory effect than resveratrol on EGF-induced cell transformation, but had less cytotoxic effects on normal nontransformed cells. Compared to resveratrol, this compound also caused cell cycle arrest in the G1 phase, but did not induce p53 activation and apoptosis. Furthermore, this compound, but not resveratrol, markedly inhibited EGF-induced phosphatidylinositol-3 kinase (PI-3K) and Akt activation. Collectively, these data suggested that the higher antitumor effect of the compound compared to resveratrol, may act through a different mechanism by mainly targeting PI-3K/Akt signaling pathways.
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PMID:Inhibition of cell transformation by resveratrol and its derivatives: differential effects and mechanisms involved. 1268 16

Resveratrol, a polyphenolic phytoalexin found in grapes, may have the potential for prevention and therapy for human cancer. We report here that resveratrol inhibits the growth of human lung carcinoma A549 cells and provides molecular understanding of this effect. Resveratrol treatment of A549 cells resulted in a concentration-dependent induction of S phase arrest in cell cycle progression. This anti-proliferative effect of resveratrol was associated with a marked inhibition of the phosphorylation of the retinoblastoma protein (pRB) and concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP, which appears to be transcriptionally upregulated and is p53- dependent. In addition, resveratrol treatment resulted in induction of apoptosis as determined by fluorescence microscopy and flow cytometric analysis. These effects were found to correlate with an activation of caspase-3 and a shift in Bax/Bcl-xL ratio more towards apoptosis. Resveratrol treatment also inhibited the transcriptional activity of nuclear transcription factor kappaB (NF-kappaB). Taken together, these findings suggest that resveratrol has strong potential for development as an agent for prevention against human lung cancer.
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PMID:Involvement of p21WAF1/CIP1, pRB, Bax and NF-kappaB in induction of growth arrest and apoptosis by resveratrol in human lung carcinoma A549 cells. 1296 97

Resveratrol and other polyphenols have anti-carcinogenic and anti-tumorigenic activities in various carcinomas. However, such studies are limited in endometrial cancer. We hypothesize that resveratrol suppresses cancer growth through modulation of cell cycle and cell growth regulatory genes. To test this hypothesis, we treated endometrial cancer cells (Ishikawa cell line) with resveratrol (1, 10, 50 and 100 micro M) for 1, 3, 5 and 7 days, and analyzed for growth signal genes (EGF and VEGF), cell cycle regulatory genes (p53 and p21), and apoptosis-related genes (bcl-2 and bax). Results of these experiments demonstrate that after resveratrol treatment, the growth of Ishikawa cells was inhibited in a dose dependent manner. The gene and protein expression data suggest that resveratrol treatment significantly decreased EGF, whereas VEGF was up-regulated in Ishiwaka cell lines. Interestingly, protein expressions of p21 and Bax were decreased, even though their mRNA expressions did not show significant changes. The present study suggests that resveratrol can suppress proliferation of Ishikawa cells through down-regulation of EGF.
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PMID:Resveratrol suppresses growth of Ishikawa cells through down-regulation of EGF. 1296

We investigated the role of resveratrol, a polyphenol rich in red wine, in cell cycle progression and apoptosis of vascular smooth muscle cells (VSMCs). Resveratrol inhibited the growth of human aortic VSMCs at concentrations as low as 1 microM. This was due to the profound dose-dependent inhibition of DNA synthesis by resveratrol. DNA synthesis was more effectively inhibited when cells were pretreated with resveratrol. Resveratrol caused a dose-dependent increase in intracellular p53 and p21(WAF1/CIP1) levels. At lower concentrations (6.25-12.5 microM), resveratrol effectively blocked cell cycle progression of serum-stimulated VSMCs without inducing apoptosis, while the higher concentration of resveratrol (25 microM) selectively induced apoptosis in the same VSMCs. Intriguingly, however, the same high concentration of resveratrol could not induce apoptosis in quiescent VSMCs. These differential biological effects of resveratrol on quiescent and proliferating VSMCs suggest that resveratrol may be capable of selectively eliminating abnormally proliferating VSMCs of the arterial walls in vivo.
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PMID:Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway. 1459 51

Resveratrol, which is found in grapes and wine, has been reported to have a variety of important pharmacological effects including anti-inflammatory, anti-platelet, and anti-carcinogenetic properties. In this study, using the human breast cancer cell line MCF-7, we have analyzed a possible mechanism by which resveratrol could interfere with cell cycle control and induce cell death. Resveratrol treatment of MCF-7 cells resulted in a dose-dependent inhibition of the cell growth and the cells accumulated at the S phase transition of the cell cycle at low concentrations, but high concentrations do not induce S phase accumulation. The anti-proliferative effects of resveratrol were associated with a marked inhibition of cyclin D and cyclin-dependent kinase (Cdk) 4 proteins, and induction of p53 and Cdk inhibitor p21WAF1/CIP. Growth suppression by resveratrol was also due to apoptosis, as seen by the appearance of a sub-G1 fraction and chromatin condensation. In addition, the apoptotic process involves activation of caspase-9, a decrease of Bcl-2 as well as Bcl-XL levels, and an increase of Bax levels.
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PMID:Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells. 1471 81

Resveratrol, a polyphenolic phytoalexin found in grapes, may have potential for the prevention and treatment of human cancer. We report here that resveratrol inhibits the growth of human prostate carcinoma DU145 cells and provide a molecular explanation of the effect. Resveratrol treatment in DU145 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death. The antiproliferative effect of resveratrol was associated with the inhibition of D-type cyclins and cyclin-dependent kinase (Cdk) 4 expression, and the induction of tumor suppressor p53 and Cdk inhibitor p21. Moreover, the kinase activities of cyclin E and Cdk2 were inhibited by resveratrol without alteration of their protein levels. Resveratrol treatment also up-regulated the Bax protein and mRNA expression in a dose-dependent manner; however, Bcl-2 and Bcl-xL levels were not significantly affected. These effects were found to correlate with an activation of caspase-3 and caspase-9. Taken together, our study suggests that resveratrol has a strong potential for development as an agent for the prevention of human prostate cancer.
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PMID:Antiproliferative effect of resveratrol in human prostate carcinoma cells. 1497 34

Multiple exposures to solar ultraviolet (UV) radiation cause critical damages that may lead to the development of several cutaneous disorders including skin cancer, the most frequently diagnosed malignancy in the USA. Therefore, efforts are needed to: (i) study the mechanism(s) of UV-mediated cutaneous damages, and (ii) design novel approaches for the management of skin cancer. 'Chemoprevention' via plant-based agents may be a useful approach for the management of neoplasia. Here, we evaluated the involvement of cell cycle regulatory molecules during resveratrol-mediated protection from multiple exposures of UVB (180 mJ/cm(2); on alternate days x 7 exposures) radiations in the SKH-1 hairless mouse skin. Resveratrol was topically applied on the skin of SKH-1 hairless mice at a dose of 10 micromol/mouse (in 0.2 ml acetone; 30 min prior to each UVB exposure). Studies were performed at 24 h following the last UVB exposure. Topical application of resveratrol resulted in significant decrease in UVB-induced bi-fold skin thickness, hyperplasia, and infiltration of leukocytes. The data from immunoblot and/or immunohistochemical analyses revealed that multiple exposure to UVB radiations causes significant upregulation in: (i) proliferating cell nuclear antigen (PCNA), a marker of cellular proliferation, and (ii) cyclin-dependent kinase (cdk)-2, -4 and -6, cyclin-D1, and cyclin-D2. Resveratrol treatment resulted in significant downregulation in UV-mediated increases in these critical cell cycle regulatory proteins. An interesting observation of this study was that resveratrol treatment resulted in a further stimulation of UVB-mediated increases in cyclin kinase inhibitor WAF1/p21 and tumor suppressor p53. Further, resveratrol was also found to cause significant decreases in UVB-mediated upregulation of: (i) the mitogen-activated protein kinase kinase, and (ii) the 42 kDa isotype of mitogen-activated protein kinase (MAPK). Thus, our data suggested that the antiproliferative effects of resveratrol might be mediated via modulation in the expression and function of cell cycle regulatory proteins cyclin-D1 and -D2, cdk-2, -4 and -6, and WAF1/p21. Our data further suggest that the modulation of cki-cyclin-cdk network by resveratrol may be associated with inhibition of the MAPK pathway. We suggest that resveratrol may be useful for the prevention of UVB-mediated cutaneous damages including skin cancer.
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PMID:Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. 1512 19


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