• BMB Reports
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• v.39 no.6
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

• Journal of Life Science
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• v.28 no.1
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• pp.37-42
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• 2018

Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.

• Journal of Life Science
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• v.29 no.10
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• pp.1080-1085
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• 2019

Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared the ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-proliferative and pro-apoptotic activities in human colorectal cancer HCT116 cells. NL, NS, and NSP decreased cell viabilities in a dose-dependent manner. All extracts increased the expression of non-steroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) as well as NAG-1 protein. And also, NL induced the expression of pro-apoptotic NAG-1 protein and PARP cleavage in a time-dependent manner. The PARP cleavage induced by NL treatment, was recovered in part by the transfection of NAG-1 siRNA. We also evaluated the effects of neferine, one of bioactive components of Nelumbo nucifera, on the proliferation and apoptosis in HCT116 cells. It also decreased cell viability in a dose-dependent manner, and induced the expression of pro-apoptotic NAG-1 protein and PARP cleavage in a dose- and time-dependent manner. In addition, PARP cleavage was recovered in part by the transfection of NAG-1 siRNA, indicating that NAG-1 may be one of the genes responsible for apoptosis induced by neferine. Overall, our findings may contribute to understand the molecular mechanisms of anti-proliferative and pro-apoptotic effects mediated by Nelumbo nucifera and neferine.

• Journal of Life Science
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• v.22 no.3
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• pp.360-365
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• 2012

We investigated the anti-proliferative activity of sulforaphane and expression changes of NAG-1 and p21 genes in response to sulforaphane treatment in human colorectal HCT116 cells. The results showed that sulforaphane decreased cell viabilities in a dose-dependent manner and induced expression of NAG-1 and p21 proteins in a dose-dependent and time-dependent manner. In addition, we found that NAG-1 expression by sulforaphane was not dependent on the presence of p53, whereas p21 expression was dependent on p53 presence. The results indicated that up-regulation of NAG-1 was not related with the activity of a dietary histone deacetylase inhibitor of sulforaphane. ATF3 induction was detected from 2 hr after sulforaphane treatment, indicating that ATF3 could be a transcription factor to up-regulate NAG-1 expression. The results of this study may help to increase our understanding of the molecular mechanism of anti-cancer activity mediated by sulforaphane in human colorectal cancer cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.4 s.48
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• pp.457-462
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• 2004

Anti-wrinkle effect of N-Acetyl-D-glucosamine (NAG) was evaluated by collagen synthesis and proliferation of normal human fibroblast. NAG was obtained by purifying deacetylated chitin which can be derived from chitin-rich crab shell. We studied in in-vitro cultures of human normal fibroblast, whether synthesis of collagens and fibroblast growth activation in these cells can be enhanced in the presence of NAG. It 야d not show any adverse effects in human shin irritation patch test. In in-vivo mouse test, it showed anti-wrinkle effect in hairless mouse (6W/F). From the HPLC analysis, the stability of NAG in the cosmetics product could be maintained for a long time. These results demonstrated that NAS can be useful anti-wrinkle cosmetic ingredient.

• Journal of the Korean Applied Science and Technology
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• v.33 no.4
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• pp.706-716
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• 2016

In this study we applied the NAG obtained by the deacetylation of chitin extracted from the shells of crabs and shrimp as cosmetic ingredient. In order to compare NAG with GLC we identified the influence of cytotoxicity, anti-inflammatory, melanin biosynthesis formation inhibition on skin cell, and we measured the effects of the change of melanin and red spots. The results show that there was not any attentive cytotoxicity on the Raw 264.7 cell and B16F10 cell, and NO formation anti-inflammatory hindrance effect induced from Raw 264.7 by LPS was slight, and NAG suppressed the increase of melanin generation concentration-dependently after we induced the melanin generation with ${\alpha}$-MSH on B16F10 and measured the melanin biosynthesis inhibition. From this result, we identified the applicability of the cosmetics containing NAG as functional cosmetic for enhancing skin-lightening because when cream containing NAG was applied to skin the index of melanin red spots showed statistically meaningful changes.

• Journal of Preventive Medicine and Public Health
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• v.26 no.1 s.41
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• pp.49-64
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• 1993

To provide the basic data for assessment of renal dysfunction related to silicosis, urinary N-acetyl-$\beta$-D-giucobarninidase(NAG) activity known as a sensitive markers for early renal damage were measured in 58 silicosis patients, and control subjects of 40 pulmonary tuberculosis Patients and 51 official workers. The results were summarized as fellows. 1. The values of blood urea nitrogen and serum creatinine in all subjects were within reference limits. But the mean value of urinary NAG activity($7.25{\pm}7.31U/g\;creatinine$) was beyond reference value and more sensitive test than others. 2. The mean value of urinary NAG activity in silicosis group was $11.98{\pm}9.05U/g\;creatinine$ and significantly higher than in tuberculosis and healthy group(p<0.01), but the mean values of NAG activity in tuberculosis and healthy group were not different(p>0.05). 3. The value of NAG activity in tuberculosis had a tendency to be increased according to severity of disease, but that was not significant(p>0.05). The value of NAG activity was increased significantly by use of nephrotoxic antituberculosis drugs(p<0.05). 4. The value of NAG activity in silicosis had a tendecy to be increased according to the size of nodule, use of nephrotoxic antituberculosis drugs and shortness of onset duration, but the increase was not significant(p>0.05). 5. After excluding the users of nephrotoxic antituberculosis drugs, the mean values of NAG activity in healthy control and in tuberculosis control were same as 3.63 U/g creatinine and 3.60 U/g creatinine, respectively. But the mean value of NAG activity in silicosis group was remarkably increased as 10.90 U/g creatinine(p<0.01). As above results, even though there are no abnormal finding in screening renal function test, silicosis can be related with renal dysfunction. And it will be very useful to apply urinary NAG activity in health management of workers exposed to dust.

• Journal of Life Science
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• v.19 no.12
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• pp.1787-1793
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• 2009

To investigate whether caffeic acid phenethyl ester (CAPE) could affect cancer cell viabilities and gene expression, human colorectal HCT116 cells were incubated with CAPE. CAPE decreased cancer cell viabilities and induced apoptosis in a dose-dependent manner. To analyse differently expressed genes by CAPE, we performed oligo DNA microarray analysis. We found that 266 genes were up-regulated more than twofold, whereas 143 genes were down-regulated more than twofold by 24 hr of treatment with $20{\mu}M$ CAPE. Among the up-regulated genes, we selected 3 genes (NSAID activated gene-1 [NAG-1], cyclin-dependent kinase inhibitor 1A [CDKN1A, p21] and growth arrest and DNA-damage-inducible alpha [GADD45A]) and performed reverse-transcription PCR to confirm microarray data. In addition, we found that CAPE increased NAG-1 gene and NAG-1 protein expression in a dose-dependent manner. And, several other phytochemicals (resveratrol, genistein, daidzein and capsaicin) also could induce NAG-1 expression in human colorectal HCT116 cells. However, CAPE was the highest inducer of NAG-1, even in low concentrations. Overall, these results imply that cancer cell death by CAPE is closely related with over-expression of NAG-1.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.977-982
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• 2003

Purpose : This study aimed to examine the excretion of various urinary proteins in children with a history of urinary tract infection(UTI), with or without vesicoureteral reflux(VUR) or reflux nephropathy, and to identify means of predicting the severity of VUR or the presence of reflux nephropathy as indicated by these markers, and to know how these markers are changed after resolution of VUR. Methods : We studied 30 children with previous UTI, without VUR and renal scarring(group I), 12 children with VUR, without evidence of renal scarring(group II), and 34 children with VUR and renal scarring(group III). 24-hour or 12-hour urine ${\beta}_2$ microglobulin(${\beta}_2$ MG), microalbumin and N-acetyl-${\beta}$-D-glucosaminidase(NAG) were measured in each child. Urinary protein excretions were analyzed according to the degree of VUR(mild VUR : a grade reflux I-III, severe VUR : a grade reflux IV-V). Cases of bilateral VUR were graded by the higher grade of reflux detected. A total of 46 children with primary VUR were followed. Among these patients, VUR was completely resolved in 16 children. Voiding cystourethrography(VCUG) and DMSA scan were performed every year. Values for urinary markers were estimated every year. Results : 24 or 12 hour urine microalbumin and NAG excretions were significantly increased in group III compared to group I(microalbumin : $27.7{\pm}26.0mg/gCr$ vs $15.0{\pm}10.7mg/gCr$, P<0.05, NAG : $15.2{\pm}18.7U/gCr$ vs $3.4{\pm}2.2U/gCr$, P<0.05). Urinary ${\beta}_2$ MG excretions were not significantly different between groups. Urinary NAG excretions were elevated in the group of children with severe VUR compared to mild VUR($26.8{\pm}27.1U/gCr$ vs $7.6{\pm}3.8U/gCr$, P<0.05). After resolution of VUR, urinary microalbumin and NAG excretions were decreased(P<0.05). Conclusion : Urinary microalbumin and NAG may be useful clinical indicators to predict the presence of reflux nephropathy and the resolution of VUR. Especially, urinary NAG excretions may be used as a possible method to predict the severity of VUR.

• Journal of Life Science
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• v.28 no.4
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• pp.415-420
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• 2018

Schisandra chinensis (Turcz.) Baill. (omija) is often used in Chinese medicine to treat various human diseases, and is known to possess various bioactive components such as schizandrin and gomisin A. In the present study, we prepared ethanol extracts of pomace of Schisandra chinensis (PSC) and investigated their effects on cell viability and expression changes of pro-apoptotic genes such as ATF3, NAG-1 and p21 in human colorectal cancer HCT116 cells. PSC significantly reduced cell viability in a dose-dependent manner, and also dramatically induced the expression of ATF3, NAG-1 and p21 genes, with resveratrol used as a positive control. We also assessed the effects of pure compound schizandrin (SZ) derived from Schisandra chinensis on cell viability and expression of pro-apoptotic genes such as ATF3, NAG-1 and p21. The results showed that SZ also decreased cell viabilities in a dose-dependent manner and increased the expression of ATF3, NAG-1 and p21 genes. In addition, apoptosis was detected in SZ-treated HCT116 cells, which was confirmed with PARP cleavage. PARP cleavage was recovered in part by the transfection of NAG-1 siRNA. The results indicate that NAG-1 is one of the genes responsible for apoptosis induced by SZ. Overall, our findings may contribute to understanding the molecular mechanisms of anti-proliferative and pro-apoptotic activities mediated by PSC and SZ.