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)

Miconazole (MIC), a promising oral antifungal agent, has been used worldwide in the treatment of superficial mycosis. In this study, we demonstrated that MIC dose dependently arrested various human cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by MIC treatment in COLO 205 cells. Electrophoretic mobility gel shift assays showed that the nuclear extracts of the MIC-treated COLO 205 cells exerted a significant binding between wild-type p53 and its consensus-binding site present in the p21/Cip1 promoter. These results suggested that the p53-associated signaling pathway is involved in the regulation of MIC-induced cancer cell growth arrest. By immunoblot analysis, we demonstrated that cyclin D3 and cyclin-dependent kinase-4 (CDK4) protein levels were inhibited by MIC treatment in the cancer cells. Significant therapeutic effect was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with MIC (50 mg/kg ip). The protein expression of p53 was significantly increased in MIC-treated tumor tissues by immunohistochemical staining and Western blotting analysis. DNA fragmentation and TUNEL assay were performed and demonstrated that apoptosis occurred in tumor tissues treated with MIC. Our study provides the novel mechanisms of antitumor effects of MIC and such results may have significant applications for cancer chemotherapy.
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PMID:Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest. 1192 74

Terfenadine (TF) is a highly potent histamine H1 receptor antagonist that in clinically effective doses is free of significant central nervous system side effects. Ketoconazole (KT) is a worldwide used oral antifungal agent with a broad spectrum of activity against both superficial and systemic mycosis. Simultaneously administration of KT and TF has been reported to induce several potent symptoms including cardiotoxicity, excitotoxicity, inhibition of blood mononuclear cells proliferation, and cardiovascular toxicity. However, the intracellular molecular mechanisms of TF-KT interactions in cells were still uncertain. In this study, we first demonstrated that TF (5-30 microM) induced apoptosis in several types of human cancer cell lines including human hepatoma (Hep G2), colorectal cancer (COLO 205), and fibroblast (CCD 922SK) cells for 24 h. The cellular responses to TF-induced apoptosis were demonstrated to be associated with the p53-signaling pathway, including induction of p53, p21/Cip1, p27/Kip1, bax protein expression and inhibition of bcl-2 protein expression. To realized the role of H1 receptor involved in TF-induced apoptosis, different H1 receptor antagonists including promethazine, mequitazine, and chlorpheniramin (50-100 microM) were administered and demonstrated that these chemicals cannot induced apoptosis through the H1 receptor signaling pathway. Interestingly, we found that the apoptotic effect of TF (2.5 microM) was significantly potentiated by KT (1 microM) treatment in Hep G2 cells through inhibition of the cytochrome p450 3A4 (CYP 3A4) activity. Such results were demonstrated by decreased of the TF activity with recombinant CYP 3A4, which prepared from baculovirus-infected insect cells. Our results provide the molecular basis of TF-KT interaction and this information should allow more rational forecasting of the risk for TF therapy during co-administration of KT.
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PMID:Ketoconazole potentiates terfenadine-induced apoptosis in human Hep G2 cells through inhibition of cytochrome p450 3A4 activity. 1224 68

Terbinafine (TB) (Lamisil), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose-dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip1 proteins were augmented. In the TB-treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB-induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53-associated signaling pathway in the TB-induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50-60%. In these tumors, increases in the p21/Cip1, p27/Kip1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo.
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PMID:In vitro and in vivo studies of the anticancer action of terbinafine in human cancer cell lines: G0/G1 p53-associated cell cycle arrest. 1279 67

Econazole (Eco), a potent broad-spectrum anti-fungal agent, has been used in the treatment of superficial mycosis. Eco is a store-operated Ca2+ channel antagonist which induces cytotoxic cell death of leukemia. However, little is known about its cytotoxic effect upon solid tumor cells. The purpose of this study is to investigate both the in vitro and in vivo molecular mechanisms of Eco-induced toxicity on colon cancer cells. We used COLO 205 cell line and nude mice xenograft model to investigate the cytotoxic effect of Eco. We demonstrated that lower doses Eco (5-20 microM) arrested human colon cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated while CDK2 and CDK4 kinase activity were significantly suppressed by Eco treatment in COLO 205 cells. At higher doses (40-60 microM), Eco induced COLO 205 cells apoptosis evidenced by ladder formation in DNA fragmentation assay and sub-G1 peak in flow cytometry analysis. Western blot analysis showed that caspases 3, 9 but not 8 were activated by high dose Eco treatment to the COLO 205 cells accompanied with cytochrome c and apoptosis-inducing factor (AIF) translocation. Significant anti-tumorigenesis effect was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with Eco 50 mg/kg intraperitoneally. Our findings highlight the molecular mechanisms underlying the Eco-induced toxicity on colon cancer cells.
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PMID:Molecular mechanisms of econazole-induced toxicity on human colon cancer cells: G0/G1 cell cycle arrest and caspase 8-independent apoptotic signaling pathways. 1591 46

Oral erythroplakia (OE) is considered a rare potentially malignant lesion of the oral mucosa. Reports entirely devoted to OE are very few, and only two reviews none of which are of recent date have been published. Only the true, velvety, red homogeneous OE has been clearly defined while the terminology for mixed red and white lesions is complex, ill-defined and confusing. A recent case control study of OE from India reported a prevalence of 0.2%. A range of prevalences between 0.02% and 0.83% from different geographical areas has been documented. OE is predominantly seen in the middle aged and elderly. One study from India showed a female:male ratio of 1:1.04. The soft palate, the floor of the mouth and the buccal mucosa is commonly affected. A specific type of OE occurs in chutta smokers in India. Lesions of OE are typically less than 1.5 cm in diameter. The etiology of OE reveals a strong association with tobacco consumption and the use of alcohol. Histopathologically, it has been documented that in OE of the homogenous type, 51% showed invasive carcinoma, 40% carcinoma in situ and 9% mild or moderate dysplasia. Recently, genomic aberrations with DNA aneuploidy has been demonstrated. p53 mutations with different degrees of dysplasia may play a role in some cases of OE. Transformation rates are considered to be the highest among all precancerous oral lesions and conditions. Surgical excision is the treatment of choice. Data on laser excision are not available. Recurrence rates seem to be high, reliable data are, however, missing. More studies on OE are strongly needed to evaluate a number of so far unanswered questions. The natural history of OE is unknown. Do OEs develop de novo or are they developing from oral leukoplakia through several intermediate stages of white/red lesions? The possible role of fungal infection (Candida micro-organisms) is not clear as is the possible role of HPV co-infection in the development of OE. More data on incidence and prevalence, biological behaviour and adequate treatment are urgently needed.
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PMID:Oral erythroplakia--a review. 1597 18

Paracoccidioidomycosis (PCMycosis) is a systemic mycosis frequently found in many regions of Latin America. Microscopically, it is characterised by granulomatous inflammation and pseudoepitheliomatous hyperplasia (PEH). This work describes the proliferation index and p53 expression by immunohistochemistry in PEH of PCMycosis, normal oral mucosa (NOM) and mild oral epithelial dysplasia (ED). Ki67 positive cells were present in the basal and parabasal layers in NOM and PEH, while in ED it was also observed in the spinous layer. Percentage of ki67 positive cells was 7.7, 28.2 and 46.0 in NOM, PEH and ED respectively. p53 was negative in NOM and in PEH it was expressed by few cells in the basal layer of only three cases. However, it was expressed in all cases of ED, in basal and parabasal layers. Although histologically PEH mimics well-differentiated squamous cell carcinoma, its proliferative pattern and p53 expression are more similar to NOM than to dysplasia. These findings, confirm PEH as a reactive process probably associated with the underlying chronic inflammation.
Mycoses 2006 Sep
PMID:Cell proliferation and p53 expression in pseudoepitheliomatous hyperplasia of oral paracoccidioidomycosis. 1692 91