• Journal of Life Science
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• v.26 no.8
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• pp.983-989
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• 2016

All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

• Journal of Life Science
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• v.19 no.7
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• pp.871-877
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• 2009

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

• Journal of Life Science
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• v.20 no.7
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• pp.977-982
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• 2010

We investigated the anti-cancer effects of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in human promyelocytic U937 cells. Gomisin N, but not gomisin A, inhibited cell growth in a concentration-dependent manner, which was associated with the induction of G1 arrest of the cell cycle. G1 arrest induced by gomisin N was correlated with down-regulation of cyclin E, cyclin-dependent kinase (Cdk) 2 and Cdk4, and a concomitant up-regulation of Cdk inhibitors such as p16 (INK4A) and p21 (WAF1/CIP1). Furthermore, gomisin N inhibited phosphorylation of retinoblastoma protein (pRB) and p130, and expression of transcription factor E2Fs. The results indicated that growth inhibition by gomisin N is related to cell cycle arrest at G1 in U937 cells and these findings suggest that gomisin N may be a useful chemotherapeutic agent.

• Journal of Life Science
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• v.27 no.12
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• pp.1507-1514
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• 2017

The purpose of this study aimed at examining the antiproliferative effect of kimchi (kimchi B) adding mistletoe extract known as an anticancer function to improve the functions of kimchi. The study investigated the antiproliferative effect through hemocytometer counts and MTT assay, apoptosis induction through DAPI staining, and mRNA expression through RT-PCR using human lung carcinoma A549 cells. The standardized kimchi (Kimchi A) was used as a control group. As a result of hemocytometer counts and the MTT assay, it was found that kimchi samples inhibited the growth of A549 cells in a concentration-dependent manner. Kimchi B induced apoptosis in A549 cells through DAPI staining. The apoptosis induced by kimchi B was associated with the increase in the expression of pro-apoptotic Bax and with the decrease in the expression of anti-apoptotic Bcl-2 and Bcl-xL. Also, kimchi B influenced the increase in the expression of p21 mRNA, but did not have the effect on the expression of p53 mRNA. In conclusion, the antiproliferative effect of kimchi B was due to apoptosis induced by increasing Bax and decreasing Bcl-2, and increasing p21. The findings will be utilized to develop kimchi with the improved function for the patients having cancer.

• Journal of Society of Preventive Korean Medicine
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• v.18 no.1
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• pp.11-21
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• 2014

Objective : This study set out to combine the treatment efficacy of Taraxacum with Dongchimi fermentation and investigate Taraxacum's effects on protection of liver cell and controlling nitric oxide(NO) through experiments, thus checking whether it had values as a physiological active matter. The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anticancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Method : The experimental materials include Taraxacum Dongchimi (TD) and Taraxacum fermented by Dongchimi (TDF). As for methodology, experiments were carried out to compare TD and TDF in components, protection effects for liver cells, anti-cancer effects on liver cells, and protection effects for brain cells in the aspects of liver function and immunity enhancement. Results : As shown in the chromatogram results, each valid component content increased in Taraxacum fermented by Dongchimi (TDF) for each time section. Of them, the valid component content at 36.80 minutes was approximately 2.7 times higher in TDF at 21.8% than in Taraxacum Dongchimi (TD) at 8.28%. TDF generated more excellent protection effects against the toxicity that caused oxidative damage to the liver cell(HepG2) with t-BHP than TD. The survival rate was low in TD of $100{\mu}g/m{\ell}$ and $300{\mu}g/m{\ell}$ and increased to 23.3% in TDF of $100{\mu}g/m{\ell}$. The survival rate was the highest at $300{\mu}M$ with a significant difference of 68.1%(P<0.05). Both TD and TDF showed effects of controlling nitric oxide production according to concentration with TDF recording a higher rate of controlling nitric oxide production than TD. There were significant differences(P<0.05) in the effects of controlling nitric oxide production at 200 ug/ml, 400 ug/ml in both groups. Especially the result TDF of $400{\mu}g/m{\ell}$ was thus similar to those of butein, the positive control group. Conclusion : The result of this studies is that Taraxacum fermented by Dongchimi (TDF) increased the valid component content compared with the simple mixture(TD). The findings clearly show that it is a material with the effects of improving immunity and liver cell protection. If fermentation methods are further developed to use it as a functional material, it will be subject to more opportunities of being used in other functional foods and make a contribution to integrated medicinal food development.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.

• The Korean Journal of Nuclear Medicine
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• v.38 no.6
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• pp.511-515
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• 2004

Purpose: The sodium-iodide symporter (NIS) expression is an important factor in determining the sensitivity of radioiodine therapy in well-differentiated thyroid cancers. Several previous studies for the expression of NIS in thyroid tissues show diverse results. To investigate whether there is difference between methods in determining the expression of NIS in thyroid tissues of patients with thyroid nodules, we measured the expression ot NIS using two different methods (RT-PCR and immunoshistochemical staining) and compared the results. Materials & Methods: We measured the expression of NIS by reverse transcriptase-polymerase chain reaction (RT-PCR) and also by immunohistochemical staining using anti-NIS antibody in thyroid cancers and other benign thyroid diseases. We compared the results of each method. We included 19 papillary carcinomas, 1 follicular carcinoma, 7 medullary carcinoma, 4 adenomas and 7 nodular hyperplasias. Results: By RT-PCR analysis, 10 of 19 papillary carcinomas expressed NIS, but 1 follicular cancer didn't express NIS. By immunohistochemical staining, 15 of 19 papaillary carcinomas express NIS, but 1 follicular lancer didn't express NIS. There was a significant correlation between the semiquautitative results of RT-PCR and immunohistochemical staining of NIS expression. (p<0.01) Conclusion: Our data demonstrated that the expression of NIS in thyroid cancers and other benign diseases investigated by RT-PCR and immunohistochemical staining correlated well each other. However, by immunohistochemical staining, more NIS expression was found.

• Journal of Life Science
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• v.15 no.4 s.71
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• pp.528-535
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• 2005

The non-enzymatic anti-oxidants and lunasin peptide from the extracts of the pepper were examined in order to utilize the discovery in natural products as cancer chemopreventive agents. The DPPH (1,1-diphenyl-2-picryl-hydrazyl) free radical scavenging activity on the fruit parts of the pepper was higher than that of the seed, but the difference was low. The Inhibition activity of xanthine/ xanthine oxidase in extracts of the seed was higher than that of the fruit and that of the seed on 20 days after flowering was the highest at the growing period. These were identified as fatty acids and phenolic compounds such as 1-eicosanol, palmitic acid, linoleic acid, linolenic acid and benzonitrile. The contents of fatty acids and phenolic compounds increased according to the time passing at the growing period. Peroxidase (POD) activity of the fruit at middle stage was high than that of other growing stages and that of the seed was the highest at later growing period. Though superoxide dismutase (SOD) activities in fruit were hish by passage of Slowing stage, the activity in seed was low. Lunasin was searched from seeds of the peppers by coomassie blue staining and western blot among them and we just found lunasin peptide from extracted protein of the pepper by western blot. In addition, we observed the contents of lunasin after flowering and confirmed to appear the lunasin at 35 days after flowering. We confirmed that lunasin is complex protein of maturing seeds. 100nM lunasin peptide in pepper showed inhibition effect on colony formation in $2\~12$ cells.

• Korean Journal of Community Nutrition
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• v.13 no.2
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• pp.263-275
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• 2008

Impaired fasting glucose (IFG) is one of significant risk factors of developing diabetes. The persons with IFG are, thus, an important target group for primary prevention of diabetes. It is well known that plasma homocysteine concentration may be increased in poor folate nutritional status. Elevated level of plasma homocysteine is considered as a marker of enhanced oxidative stress. In addition, the protective effect against oxidative stress may be diminished in poor antioxidative nutrient status as vitamin C. It is, therefore, important to maintain adequate nutritional status of folate and vitamin C in the patients with type 2 diabetes or IFG. This study was performed to determine the effects of supplementation of folic acid or vitamin C on plasma concentrations of homocysteine, oxidized LDL, and lipids and on the activity of plasma anti-oxidative enzyme in patients with IFG. A total of 97 patients with IFG were participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folatesupplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A were received 1,000 mg of vitamin C, and those in FA were given 1 mg of folate plus 1,000 mg of vitamin C daily for 4 weeks. No change in plasma concentrations of vitamin C, lipids, and oxidized LDL and the activity of GSH-Px were observed in vitamin C-supplemented group (A + FA) and folate-supplemented group (F + FA) compared to the placebo group (C + A). Only the folate-supplemented group (F + FA) had significantly increased average serum folate concentration and lowered plasma homocysteine concentration compared to the placebo group (C + A). Thus, it should be recommended the patients with IFG to increase folate intake through diets and, if it is not sufficient, to take folic acid supplements to prevent the development of complications induced by hyperhomocysteinemia as well as oxidative stress.

• Korean Journal of Environmental Biology
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• v.27 no.1
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• pp.58-65
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• 2009

The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.