Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-8 (Il-8) and IL-10 are cytokines associated with the Epstein Barr Virus (EBV), which is linked with nasopharyngeal cancer (NPC). In the present study, we investigated the endogenous production of IL-8 and IL-10 in vitro by two EBV-positive NPC cell lines, viz., HK1 and CNE-2. IL-8 was expressed by both cell lines although the level of IL-8 was 2-fold higher in supernatant from HK1 cells. Incubation with hypericin, a natural photosensitizer increased IL-8 significantly but only in HK1 cells. Hypericin-based photodynamic therapy (PDT) did not alter the expression of IL-8 levels. Il-10 was not constitutively expressed in either cell line and could not be induced by PDT. It is interesting that PDT which is known to upregulate IL-8 transcription via reactive oxygen species and activate the IL-10 promoter did not alter IL-8 levels in either of the NPC cell lines nor induced the production of IL-10.
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PMID:Endogenous expression of interleukin-8 and interleukin-10 in nasopharyngeal carcinoma cells and the effect of photodynamic therapy. 1206 Aug 53

Photoactivation of hypericin is known to generate singlet oxygen and superoxide anion radicals. Reactive oxygen species (ROS) produced by photodynamic therapy (PDT) has the capacity to induce oxidative damage and tumor destruction. We have previously shown that hypericin-PDT induces tumor shrinkage and regression in the human nasopharyngeal cancer (NPC)/HK1 murine tumor model. In this extended study, we show by electron microscopy that subcutaneously implanted HK1 NPC cells from Balb/c nude mice perished by cell necrosis with hypericin-PDT treatment. There was evidence of cytoplasmic swelling accompanied by loss of cell membrane integrity and autophagic vacuolization of cytoplasm but no nuclear changes. There was also no significant difference in the apoptotic index of control and PDT-treated tumors, when analyzed by in situ end labeling of DNA strand breakage to detect apoptosis. This further supports the observation that cell death in PDT-treated NPC/HK1 tumors was by necrosis. Lipid peroxidative stress analyzed by the malonaldehyde assay was significantly elevated in PDT-treated cells. However, PDT had no effect on the activity of superoxide dismutase, an intracellular antioxidant enzyme. The findings show that hypericin-PDT of nasopharyngeal tumors in vivo induces tumor necrosis with accompanying lipid peroxidation.
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PMID:Hypericin-mediated photodynamic therapy induces lipid peroxidation and necrosis in nasopharyngeal cancer. 1453 82

Nasopharyngeal carcinoma is a common cancer in South-East Asia, especially among people of Chinese origin. In this report, we investigate the effects of quercetin on the growth of wild-type and mutant p53 nasopharyngeal carcinoma cell lines, HK1 and CNE2 respectively. The wild-type p53 HK1 was more susceptible to growth inhibition by quercetin than the mutant p53 CNE2. The ID50 values for HK1 and CNE2 were 35.0 and 54.5 microM respectively. Cell growth arrest was initiated by the up-regulation of retinoblastoma gene expression, resulting in cell cycle arrest in either the G2/M or G0/G1 phase at 14.8 and 52.1 microM quercetin respectively regardless of the p53 status. Flow cytometry experiments revealed that quercetin-induced apoptosis during the first 24 h followed by necrosis in both HK1 and CNE2. Western blot experiments confirmed that cytotoxic killing of HK1 and CNE2 by quercetin was mediated by the up-regulation of pro-apoptotic protein Bad, caspase-3 and -7, resulting in cell death by apoptosis. Our study demonstrates that quercetin inhibits cell growth of nasopharyngeal carcinoma cell lines HK1 and CNE2 by inhibiting cell cycle progression to S phase. Quercetin is also able to induce apoptosis and necrosis in these cells regardless of the p53 status.
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PMID:Quercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressions. 1476 29

Singlet oxygen (1O2) generated by ultraviolet A irradiation has been reported to induce cytokine-dependent Matrix metalloproteinase-1 (MMP-1) expression in dermal fibroblasts. In the present study, we analyzed the effect of hypericin-based photodynamic therapy (PDT) on MMP-1 expression in two nasopharyngeal cancer (NPC) cell lines and an animal tumor model. MMP-1 protein and mRNA expression were evaluated by Western blot analysis and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) respectively. Photoactivation of hypericin, a polycyclic phenanthroperylenedione, elicited an increase in MMP-1 protein and mRNA expression in well differentiated HK1 and poorly differentiated CNE-2 NPC cells in vitro. Similarly, there was up-regulation of MMP1 mRNA expression in hypericin-PDT-treated NPC/HK1-tumors. To our knowledge, this is the first time that modulation of MMP-1 expression has been demonstrated as a photodynamic effect of hypericin in NPC cells. This has clinical implications as MMP-1 is known to play an essential role in the biological process of matrix remodeling.
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PMID:Modulation of Matrix metalloproteinase-1 in nasopharyngeal cancer cells by photoactivation of hypericin. 1476 50

Photodynamic therapy (PDT) is a new modality of treatment for cancer. Hypericin is a photosensitizer, which is known to generate reactive oxygen species upon activation with light. We observed that photoactivated hypericin induces the generation of reactive oxygen intermediates in nasopharyngeal cancer (NPC) cells in vitro. There was also significant reduction of Glutathione S-transferase (GST) activity in HK1 and CNE-2 NPC cells and in tumor tissues from the NPC/HK1 murine tumor model by hypericin-mediated PDT. As antioxidants protect cells against phototoxicity, down-regulation of GST activity would potentiate the efficacy of hypericin-PDT treatment.
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PMID:Photoactivation of hypericin down-regulates glutathione S-transferase activity in nasopharyngeal cancer cells. 1507 26

Biological functions of metallothionein (MT) proteins which are encoded by 10 functional MT isoforms, include cell proliferation, differentiation and apoptosis. The aim of this study was to compare the relative expression levels of functional MT mRNA isoforms in three nasopharyngeal cancer (NPC) cell lines with laryngeal carcinoma and embryonic lung cell lines by quantitative real-time RT-PCR. All the NPC lines exhibited expression of the MT-2A transcript, whereas the MT-1E isoform was expressed in well differentiated HK1 and moderately differentiated TW01 but not in poorly differentiated CNE2 cells. Interestingly, TW01 and HEp-2 laryngeal cancer cells exhibited similar expression profiles with both MT-1E and MT-2A isoforms being detected at levels below those of MRC-5 embryonic lung fibroblasts. Functional studies of the MT-2A isoform by down-regulating expression of this gene with MT-2A antisense oligonucleotide in CNE2 cells, showed a reduction in cell viability and proliferation. These findings may provide valuable information in the search for novel therapeutic strategies against NPC.
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PMID:Differential expression of metallothionein isoforms in nasopharyngeal cancer and inhibition of cell growth by antisense down-regulation of metallothionein-2A. 1558 13

Cytokines induce inflammatory and immune responses in tumors after photodynamic therapy (PDT). Since there are no reports of IL-6 in nasopharyngeal cancer (NPC) cells following PDT, we evaluated IL-6 expression in two different NPC tumors after hypericin mediated PDT. Interleukin-6 transcription was significantly upregulated in PDT-treated CNE-2 poorly differentiated cells but not in HK1 well differentiated cells. In vivo, IL-6 mRNA expression was elevated in PDT-treated CNE-2 tumors but not in HK1 tumors. In conclusion, the study elucidated that the cell type, degree of histological differentiation and the basal expression of the cytokine influence the cytokine response following PDT.
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PMID:Hypericin-mediated photodynamic therapy elicits differential interleukin-6 response in nasopharyngeal cancer. 1593 50

The Y-Box binding protein, YB-1, belongs to a group in the DNA and RNA binding protein family. YB-1 is known to be expressed in a number of different cancers and reported to protect cells against DNA-damaging agents such as ultraviolet light. The purpose of this study was to determine if YB-1 levels are altered in photodynamic therapy (PDT)-treated nasopharyngeal cancer (NPC) cells. In this report, we show for the first time that YB-1 is expressed at both the mRNA and protein levels in well-differentiated NPC in vivo. YB-1 mRNA expression in tumor tissues from a murine well-differentiated HK1/NPC model showed no significant difference in mRNA levels following hypericin-PDT. Localization of the YB-1 protein by immuno-histochemistry revealed the presence of cytoplasmic YB-1 in the more mature and better differentiated cells of the untreated group, as well as cells that survived PDT treatment. Expression of the YB-1 protein may possibly influence the cellular stress response to hypericin-PDT and protect the cells from phototoxicity.
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PMID:Expression of Y-Box binding protein-1 following hypericin-mediated photodynamic therapy in well-differentiated nasopharyngeal cancer in vivo. 1621 Dec 56

Photoactivation of hypericin is known to generate reactive oxygen species and induce phototoxic effects. However, modulation of the cellular antioxidant defense would influence the extent and severity of the photodynamic effects. We have previously shown that hypericin-mediated photodynamic therapy (PDT) induced a significant reduction of Glutathione S-transferase activity. In this study, we investigated the phototoxic effects of hypericin-mediated PDT in nasopharyngeal cancer (NPC) in vitro and analyzed the expression of metallothionein (MT), a family of potential free radical scavengers. HK1 NPC cells were subjected to PDT treatment in vitro, and the effects on cell death were analyzed by flow cytometry (using propidium iodide and Annexin V staining) and transmission electron microscopy. The expression profile of MT-1E and MT-2A isoforms (the only functional MT isoforms expressed in HK1 NPC cells) were determined by quantitative real-time RT-PCR. The results showed that hypericin PDT induced necrotic cell death as evidenced by the absence of a subdiploid peak and decreased Annexin-V fluorescence. Ultrastructural examination verified the presence of cell necrosis. There was a significant up-regulation of MT-1E and MT-2A isoforms six hours following PDT, with an approximately 50-fold rise in the expression level of MT-1E and a 15-fold increase of MT-2A. Hence, despite the up-regulation of MT, cells still succumbed to PDT-induced necrosis. It appears that the oxidative stress induced by PDT overwhelmed the antioxidant defense mechanism such as the alteration of MT levels in tumor cells.
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PMID:Differential up-regulation of metallothionein isoforms in well-differentiated nasopharyngeal cancer cells in vitro by photoactivated hypericin. 1708 67

Recently, we have shown that hypericin-mediated photodynamic therapy (PDT) is a promising modality for the treatment of nasopharyngeal cancer (NPC). The present study evaluated the expression of matrix metalloproteinase-9 (MMP-9) following hypericin-PDT in well-differentiated HK1 NPC cells. Down-regulation of MMP-9 by hypericin-PDT was observed at the mRNA level in HK1 cells in vitro and in vivo and at the protein level in vitro. Transcriptional activities of the activator protein-1 (AP-1) and nuclear factor (NF)-kappaB regulatory elements were inhibited by PDT. We also found that PDT reduced secreted granulocyte-macrophage colony stimulating factor (GM-CSF), which is known to activate transcription of NK-kappaB and AP-1. However, incubation of untreated HK1 cells with exogenous GM-CSF abrogated the reduction of MMP-9 production in hypericin-PDT-treated cells. It would appear that PDT downregulates MMP-9 expression via inhibition of GM-CSF production, which in turn modulates AP1/NF-kappaB transcriptional activities. Suppression of MMP-9 by hypericin-PDT may have therapeutic implications.
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PMID:Hypericin photoactivation triggers down-regulation of matrix metalloproteinase-9 expression in well-differentiated human nasopharyngeal cancer cells. 1738 73


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