• Journal of Life Science
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• v.24 no.8
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• pp.837-842
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• 2014

The purpose of this study was to investigate the effect of Brunfelsia grandiflora ethanol extract (BGEE) on the induction of autophagy via regulation of SIRT1 expression and p53 activation in a human lung fibroblast cell line, IMR 90. BGEE at a concentration of $5{\mu}g/ml$ or more exhibited a cytotoxic effect on IMR 90 cells. For the first time, this study showed that BGEE induces autophagy in normal human lung fibroblasts. BGEE also increased the expression level of beclin-1 at $2.5{\mu}g/ml$ or less and Atg7 at $5{\mu}g/ml$, both of which are known to be involved in the induction of autophagy. In addition, BGEE modulated the expression of other proteins related to autophagy in normal human lung fibroblasts. The expression levels of p53 and p-p53, an active form of p53, were decreased in the presence of BGEE at a noncytotoxic concentration. In contrast, the expression level of SIRT1 was increased in human lung fibroblasts treated with BGEE at a noncytotoxic concentration. Moreover, SA-${\beta}$-Gal staining, an aging marker, was reduced in the normal human lung fibroblasts treated with BGEE. These findings suggest that BGEE promotes the induction of autophagy and antiaging through the modulation of p53 and SIRT1 in human lung fibroblasts.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.73-80
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• 2002

Purpose : Tumor growth in a given neoplasm is the net result of cell proliferation and cell loss, and apoptosis is the most significant component of continuous cell loss in most tumors. In this study, we examined non-Hodgkin's lymphoma (NHL, n=67) immunohistochemically for the presence of Bcl-2 oncoprotein and P53 protein and compared apoptotic indices (Als) and Ki-67 proliferative indices (percentages of Ki-67 positive cells). Materials and Methods : 67 patients with NHL were evaluated : 3 low-grade and 64 intermediate-grade. The phenotype was determined in 65 cases : 47 $(70\%)$ were B cell type and 18 $(27\%)$ were T ceil type. Als and Ki-67 proliferative indices were determined immunohistochemically and the overexpression of P53 and Bcl-2 protein were also evalutated. Results : The overexpressions of Bcl-2 protein and P53 protein were found in $40\%$ (26/65) and $31\%$ (20/65). The Al ranged from $0\%\;to\;15\%$ (mean 2.16, median 1.2). Cellular Bcl-2, which counteracts apoptosis, was significantly (p=0.005) associated with Als. Ki-67 proliferative indices ranged from $1\%\;to\;91\%$ (mean 55.4), and P53 was significantly (p=0.000) associated with Ki-67 proliferative indices. A positive correlation between Als and Ki-67 proliferative indices was revealed (p=0.012) in Bcl-2 positive patients. Conclusion : In NHL, we observed a correlation between Als and Bcl-2 expression, between Ki-67 proliferative indices and P53 expression, and between Als and Ki-67 proliferative indices in Bcl-2 positive patients. Our results suggest that cell apoptosis may be inseparable from cell proliferation during tumor growth.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• BMB Reports
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• v.44 no.12
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• pp.782-786
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• 2011

Aberrant GAPDH expression following S-nitrosoglutathione (GSNO) treatment was compared in HepG2 cells, which express functional p53, and Hep3B cells, which lack functional p53. The results of Western blotting and fluorescent immunocytochemistry revealed that nuclear translocation and accumulation of GAPDH occur in both HepG2 and Hep3B cells. This finding suggests that p53 may not be necessary for the GSNO-induced translocation of GAPDH to the nucleus during apoptotic cell death in hepatoma cells.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.265-279
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• 1996

Damage produced by radiation elicits a complex response in mammalian cells, including growth rate changes and the induction of a variety of genes associated with growth control and apoptosis. At doses of 10,000 cGy or greater, the exposed individual was killed in a matter of minutes to a couple of days, with symptoms consistent with pathology of the central nervous system(CNS) including degenerative changes. The nature of the damage in irradiated cells underlies the unique hazards of ionizing radiation. Radiation injury to CNS is a rare event in clinical medicine, but it is catastrophic for the patient in whom it occurs. The incidence of cerebral necrosis has been reported as high as 16% for doses greater than 6,000 cGy. In this study, the effect of radiation on brain tissue was studied in vivo. Jun and p53 genes in the rat brain were induced by whole body irradiation of rat with 600Co in doses between 1 Gy and 100 Gy and analyzed for expression of jun and p53 genes at the postirradiation time up to 6 hours. Northern analyses were done using 1.8 Kb & 0.8 Kb-pGEM-2-JUN/Eco RI/Pst I fragments, 2.0 Kb-php53B/Bam HI fragment and ,1.1 Kb-pBluescript SK--ACTIN/Eco RI fragment as the digoxigenin or [${\alpha}^{32}P$] dCTPlabeled probes for Jun, p53 and ${\beta}$-actin genes, respectively. Jun gene seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 1 hour after irradiation of $^{60}$Co in dose of 30 Gy. Jun was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in doses of 1 Gy and 10 Gy. After irradiation of $^{60}$Co in dose between 20 Gr and 100 Gy, the expression of Jun was however increased to peak in 2 hours and decreased thereafter. p53 gene in this study also seemed to be expressed near the threshold levels in 1 hour after irradiation of $^{60}$Co in dose less than 1 Gy and was expressed in maximum at 6 hours after irradiation of $^{60}$Co in dose of 1 Gy, p53 was expressed increasingly with time until 5 or 6 hours after irradiation of $^{60}$Co in dose between 1 Gy and 40 Gy. After irradiation of $^{60}$Co in doses of 50 Gy and 100 Gy, the expression of p53 was however increased to peak in 2 hours and decreased thereafter. The expression of Jun and p53 genes was not correlative in the brain tissue from rats. It seemed to be very important for the establishment of the optimum conditions for the animal studies relevant to the responses of genes inducible on DNA damage to ionizing radiation in mammalian cells. But there are many limitations to the animal studies such as the ununiform patterns of gene expression from the tissue because of its complex compositions. It is necessary to overcome the limitations for development of in situ Northern analysis.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.483-489
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• 2009

Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.

• BMB Reports
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• v.32 no.1
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• pp.45-50
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• 1999

We previously found three transcription factor-binding motifs in the rat p53 promoter. They are two recognition motifs of NF1-like protein (NF1-like element 1: -296 ~ -312, NF1-like element 2: -195 ~ -219) and a bHLH protein binding element (-142 ~ -146). In this study, we investigated the DNA-protein complex formation of the three elements with nuclear extracts from both normal and regenerating liver to find the element involved in the induced transcription of p53. The level of each DNA-protein complex on NF1-like and bHLH motifs was not changed. Instead, a new element located at -264 ~ -284 was detected in the DNase I footprinting assay with regenerating nuclear extract. This element has partial homology to the AP1 consensus motif. However, the competition studies with diverse oligonucleotides suggest that the binding protein is not AP1. An in vitro transcription assay shows that this element is important for the transcriptional activation of the rat p53 promoter. Therefore, for the induced transcription of the rat p53 promoter, the-264 ~ -284 region is required in addition to two NF1-like and one bHLH motif.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6739-6742
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• 2013

Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

• Tuberculosis and Respiratory Diseases
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• v.76 no.6
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• pp.284-288
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• 2014

Malignant mesothelioma (MM) is the aggressive tumor of serosal surfaces. There are crude pathogenetic results regarding the biology of MM. Coordinated upregulations of p53 gene expression are shown in malignancies. We believed that there are changes in the p53 expression with transformation from reactive hyperplasia to MM. A 65-year-old male was admitted the hospital because of left pleuritic chest pains in 2004. Chest computed tomography (CT) results showed left pleural effusions with loculation and pleural thickening. Pathologic findings revealed reactive mesothelial hyperplasia. In 2008, the patient again felt left pleuritic chest pains. Chest CT showed progressive thickening of the left pleura. Pathologic diagnosis was atypical mesothelial hyperplasia. In 2011, chest CT showed progressive thickening of his left pleura. He was diagnosed with well-differentiated papillary mesothelioma. Serial change was analyzed by immunohistochemical staining for p53 of pleural tissues. There were no remarkable changes in p53 expressions during the transformation to MM.

• BMB Reports
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• v.44 no.3
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• pp.211-216
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• 2011

Vitamin C (VC) is an important antioxidant and enzyme co-factor that works by stimulating the immune system and protecting against infections. It is well known that melanoma cells are more susceptible to VC than any other tumor cells. However, the role of VC in the treatment of colon cancer has not been studied. Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer, while the role of p53 in CDDP-induced cell death has been stressed. Using cell growth assays, morphological methods, Western blotting, flow cytometry, and DNA fragmentation analysis, we measured the expression of p53 level involved in the effect of VC on CDDP-induced apoptosis of HCT116, a human colon cancer cell line. CDDP plus VC treatment resulted in significantly increased apoptosis along with upregulation of p53 compared to untreated cells and/or CDDP-treated cells. These results suggest that VC enhanced CDDP sensitivity and apoptosis via upregulation of p53.