PURPOSE: The events of cell stress and cell death are linked, with the heat shock proteins (Hsps) induced in response to stress appearing to function at key regulatory points in the control of apoptosis. The purpose of this study was to investigate the effect of arisostatins A on the Hsp70 expression and signal mechanism of its transcription. MATERIALS AND METHODS: We used natural arisostatins A produced by Actinomycete, in Caki cells. We measured the growth rate of cell using trypan blue staining, and the induction of the transcriptional levels of Hsp70 with arisostatins, which was quantified by reverse transcript-polymerase chain reaction (RT-PCR) and transiently transfecting cells with a Hsp70. The induction of the transcriptional levels of Hsp70 with arisostatins A was quantified by RT-PCR and transiently transfecting cells with a Hsp70 promoter-luciferase reporter plasmid. RESULTS: Arisostatins A-induced Hsp70 up-regulation was not prevented by the overexpression of peroxiredoxinI (PrxI), PrxII or treatment of superoxide dismutase and catalase. However, the arisostatins A-mediated expression of Hsp70 was reduced significantly in Caki cells treated by the antioxidant, N-acetylcystein. Inhibition of the Janus tyrosine kinase (JAK) activity with AG490 did not inhibit the arisostatins A-induced Hsp70 up-regulation, suggesting that JAK is not associated with the arisostatins A-mediated Hsp70 expression. The mechanism of Hsp70 induction depends on the activation of heat shock factor-1. However, arisostatins A did not effect the change in the expression levels of heat shock factor-1. CONCLUSIONS: These findings suggested that Hsp directly regulates specific stress-responsive signaling pathways, which may antagonize the signaling cascades that result in apoptosis.
Apoptosis ; Carcinoma, Renal Cell* ; Catalase ; Cell Death ; Cell Line* ; Heat-Shock Proteins* ; Hot Temperature* ; HSP70 Heat-Shock Proteins* ; Plasmids ; Protein-Tyrosine Kinases ; Shock ; Superoxide Dismutase ; Trypan Blue ; Up-Regulation

No abstract available.
Apoptosis* ; Carcinoma, Renal Cell* ; Cell Line* ; Interferon-gamma*

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Presented here in are two cases of chronic subdural hematoma in children which were spontaneously resolved. The first case has developed as the complication of a ventriculoperitoneal shunt in bilateral cerebral convexities of a 14-year-old boy while in the other case, the hematoma was developed in the posterior fossa of a 19 days-old neonate are complication of delivery. The etiology, clinical couse, treatment and mechanism of spontaneous resolution of chronic subdural hematomas in children and adult are discussed.
Adolescent ; Adult ; Child* ; Hematoma ; Hematoma, Subdural, Chronic* ; Humans ; Infant, Newborn ; Male ; Ventriculoperitoneal Shunt

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.
Apoptosis* ; Caspase 3 ; Cell Cycle Proteins ; Cell Cycle* ; Cell Death ; Complementary Therapies ; Curcuma ; Curcumin* ; Cytochromes c ; Cytosol ; Down-Regulation ; Gelatin ; Neoplasm Metastasis* ; Plants ; Plants, Medicinal ; Reactive Oxygen Species ; Rhizome ; Vitis

BACKGROUND: Malignant gliomas are the most common primary tumors in the central nervous system. METHODS: We investigated the combined effect of PG490 and LPS on the induction of the apoptotic pathway in human astroglioma cells. RESULTS: Treatment of U87 cells with combination of 50 nM of PG490 and 50microgram/ml of LPS resulted in increased internucleosomal DNA fragmentation, cleavage of PLC-gamma1, and down- regulation of cIAP1 and XIAP. The combination of LPS and PG490 treatment-induced apoptosis is mediated through the activation of caspase, which is inhibited by the caspase inhibitor, z-VAD-fmk. Also, release of cytochrome c was found in PG490 and LPS- cotreated U87 cell. CONCLUSION: Taken together, combination of PG490 and LPS appears to be a potent inducer of apoptosis in astrogliaoma cells, and might have some benefit in the treatment of glioma patients.
Apoptosis* ; Astrocytoma* ; Central Nervous System ; Cytochromes c ; DNA Fragmentation ; Glioma ; Humans*