• Toxicological Research
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• 제19권3호
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• pp.161-172
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• 2003

Explanted mammalian cells perform a limited number of cell division in vitro and than are arrested in a state known as replicative senescence. Such cells are irreversibly blocked, mostly in the G1 phase of cell cycle, and are no longer sensitive to growth factor stimulation. Thus replicative senescence is defined as a permanent and irreversible loss of replicative potential of cells. For this characteristic, replicative senescence seems to evolve to protect mammalian organism from cancer. However, senescence also contributes to aging. It seems to decrease with age of the cell donor and, as a form of cell senescence, is thought to underlie the aging process. Extensive evidence supports the idea that progressive telomere loss contributes to the phenomenon of cell senescence. Telomeres are repetitive structures of the sequence (TTAGGG)n at the ends of linear chromosomes. It has been shown that the average length of telomere repeats in human somatic cells decreases by 30∼200 bp with each cell division. It is generally believed that when telomeres reach a critical length, a signal is activated to initiate the senescent program. This has given rise to the hypothesis that telomeres act as mitotic clocks to regulate lifespan. One proposes that cumulative oxidative stress, mainly reactive oxygen species generated from mitochondria, may mainly cause telomere shortening, accelerating aging. Here, the biological importance and mechanism of replicative senescence were briefly reviewed. Also it was summarized that how oxidative stress affects replicative senescence and telomere shortening.

• 생약학회지
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• 제52권1호
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• pp.34-40
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• 2021

Proliferation and maintain of dermal papilla during progression of hair-cycle are crucial to the duration of anagen and regulated by diverse signaling pathway such as PI3K/Akt/Wnt/β-catenin pathway. In this study, we investigated the effects and mechanisms of Viola verecunda on dermal papilla cells. Treatment of dermal papilla cells with whole plant extract of V. verecunda resulted in cell proliferation, which was accompanied by up-regulation of cyclin D1, phospho (ser780)-pRB and cdc2 p34, and down-regulation of p27kip1. V. verecunda extract also promoted the levels of phospho (ser473)-Akt and phospho (ser780)-pRB in a time-dependent manner. Inhibition of PI3K/Akt by Wortmannin suppressed progression of cell-cycle, thereby attenuated the increases in proliferation of dermal papilla cells by V. verecunda extract. We further investigated Wnt/β-catenin pathway with respect to the effects of V. verecunda extract on the proliferation of dermal papilla cells. Treatment with V. verecunda extract results in up-regulation of Wnt/β-catenin proteins such as phospho (ser9)-GSKβ, phospho (ser552)-β-catenin and phospho (ser675)-β-catenin. In addition, Wortmannin abrogated V. verecunda extract mediated up-regulation of cdc2 p34 and down-regulation of p27kip1. These finding reveal that the proliferative effect of V. verecunda mediated by alteration of cell-cycle via activating PI3K/Akt/Wnt pathway in dermal papilla cells.

• Bulletin of the Korean Chemical Society
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• 제25권8호
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• pp.1121-1122
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• 2004

• 대한한방부인과학회지
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• 제19권2호
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• pp.214-225
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• 2006

Purpose : This study was aimed to investigate the inhibitory effect of Corydalis Tuber on the proliferation of human uterine leiomyoma cell and the expression of gene related the mechanism of cell apoptosis. Methods : We counted the number of suvival cells treated with indicated concentration of Corydalis Tuber and investigated cell viability by MTS assay. Furthermore, flow cytometric analyis were used to dissect between necrosis and apoptosis related with cell cycle and then we observed the differential gene expression by western blot analysis. Results : 1) The inhibitory effect on the proliferation of uterine leiomyoma cell treated with Corydalis Tuber was increased in a concentration and time proportional. 2) The result of flow cytometry analysis, subG1 phase arrest related cell apoptosis was not investigated in uterine leiomyoma cell treated Corydalis Tuber but showed G2/M phase prolongation. 3) The gene expression of p27, p21 related cell cycle was increased according to increasing concentration, but p53 was not exchanged. 4) The dephosphorylation of pRb gene were increased dependent on treatment concentration and pro-caspase 3, CDK4 were not exchanged. Conclusion : This study showed that Corydalis Tuber have the inhibitory effect on the proliferation of human uterine leiomyoma cell but the effect was thoughted no relationship with apoptosis. The inhibitory effect was suggested that dephosphorylation of pRb gene induced with increasing p21, p27 prolonged cell division in G2/M phase.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.211-217
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• 2011

Panax ginseng CA Meyer, a herb from the Araliaceae, has traditionally been used as a medicinal plant in Asian countries. Ginseng extract fermented by ginsenoside-${\beta}$-glucosidase treatment is enriched in ginsenosides such as Rh2 and Rg3. Here we show that a fermented ginseng extract, BST204, has anti-proliferative and anti-invasive effects on HT-29 human colon cancer cells. Treatment of HT-29 cells with BST204 induced cell cycle arrest at $G_1$ phase without progression to apoptosis. This cell cycle arrest was accompanied by up-regulation of tumor suppressor proteins, p53 and p21$^{WAF1/Cip1}$, down-regulation of the cyclin-dependent kinase/cyclins, Cdk2, cyclin E, and cyclin D1 involved in $G_1$ or $G_1/S$ transition, and decrease in the phosphorylated form of retinoblastoma protein. In addition, BST204 suppressed the migration of HT-29 cells induced by 12-O-tetradecanoylphorbol-13-acetate, which correlated with the inhibition of metalloproteinase-9 activity and extracellular signal-regulated kinase activity. The effects of BST204 on the proliferation and the invasiveness of HT-29 cells were similar to those of Rh2. Taken together, the results suggest that fermentation of ginseng extract with ginsenoside-${\beta}$-glucosidase enhanced the anti-proliferative and the anti-invasive activity against human colon cancer cells and these anti-tumor effects of BST204 might be mediated in part by enriched Rh2.

• 한국한의학연구원논문집
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• 제18권1호
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• pp.75-84
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• 2012

Objective : The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of Doxorubicin (DOX) in human breast adenocarcinoma cells (MCF-7). Method : We used human breast adenocarcinoma cell line, MCF-7 cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle analysis was done the MCF-7 cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with 100 ${\mu}g/ml$ Sophorae Radix. Result : Sophorae Radix inhibited the growth of MCF-7 cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in MCF-7 cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with DOX markedly inhibited the growth of MCF-7 cells compared to Sophorae Radix or DOX alone. After 3 days treatment of MCF-7 cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Conclusion : Our findings provide insight into unraveling the effects of Sophorae Radix in human breast adenocarcinoma cells and developing therapeutic agents against breast cancer.

• Journal of Periodontal and Implant Science
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• 제49권3호
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• pp.138-147
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• 2019

Purpose: Several studies have shown that the oral cavity is a secondary location for Helicobacter pylori colonization and that H. pylori is associated with the severity of periodontitis. This study investigated whether H. pylori had an effect on the periodontium. We established an invasion model of a standard strain of H. pylori in human periodontal ligament fibroblasts (hPDLFs), and evaluated the effects of H. pylori on cell proliferation and cell cycle progression. Methods: Different concentrations of H. pylori were used to infect hPDLFs, with 6 hours of co-culture. The multiplicity of infection in the low- and high-concentration groups was 10:1 and 100:1, respectively. The Cell Counting Kit-8 method and Ki-67 immunofluorescence were used to detect cell proliferation. Flow cytometry, quantitative real-time polymerase chain reaction, and western blots were used to detect cell cycle progression. In the high-concentration group, the invasion of H. pylori was observed by transmission electron microscopy. Results: It was found that H. pylori invaded the fibroblasts, with cytoplasmic localization. Analyses of cell proliferation and flow cytometry showed that H. pylori inhibited the proliferation of periodontal fibroblasts by causing G2 phase arrest. The inhibition of proliferation and G2 phase arrest were more obvious in the high-concentration group. In the low-concentration group, the G2 phase regulatory factors cyclin dependent kinase 1 (CDK1) and cell division cycle 25C (Cdc25C) were upregulated, while cyclin B1 was inhibited. However, in the high-concentration group, cyclin B1 was upregulated and CDK1 was inhibited. Furthermore, the deactivated states of tyrosine phosphorylation of CDK1 (CDK1-Y15) and serine phosphorylation of Cdc25C (Cdc25C-S216) were upregulated after H. pylori infection. Conclusions: In our model, H. pylori inhibited the proliferation of hPDLFs and exerted an invasive effect, causing G2 phase arrest via the Cdc25C/CDK1/cyclin B1 signaling cascade. Its inhibitory effect on proliferation was stronger in the high-concentration group.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 발생공학 국제심포지움 및 학술대회 발표자료집
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• pp.3-4
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• 2001

Normal cells proliferate generally a limited number doublings in culture and only rarely have they been shown to overcome cellular senescence and crisis stages, and immortalize spontaneously. I have established a number of non-chemically and non-chemically immortalized embryo fibroblastic (EF) cell lines in continuous cell culture. These include the spontaneously immortalized cell line, DF-1 and several immortal EF cell lines derived from various embryonic tissues. I have previously demonstrated that all of the immortal EF cells established have rapid cell proliferation capacity compared to primary EF cells, presumably due to the deregulation of cell cycle regulators such as p53, E2F-1 and the numerous cyclins. DF-1 cells, in particular, were shown to proliferate more rapidly under normal culture conditions compared to other immortal EF cells, implicating other mechanisms may be important for regulating their growth. The possible mechanism(s) underlying the accelerated growth of DF-1 cells will be addressed in this study. (omitted)

• 한국환경성돌연변이발암원학회지
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• 제22권1호
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• pp.54-59
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• 2002

We have used cDNA microarray hybridization to identify gene regulated in response to gamma-irradiation in U-937 cell. The cDNA-chip was composed entirely of 1,000 human cancer related gene including apoptosis and angiogenesis etc. In gamma-irradiated U-937 cell, highly charged protein, ribosomal protein L32, four and a half LIM domains 3, lipocalin 2 (oncogene 24p3) and interleukin 15, ataxia telangiectasia mutated (includes complementation groups A, C and D) genes showed increased level of its transcription, and cell division cycle 25A, dihydrofolate reductase, topoisomerase (DNA) II beta(180kD), kinase suppressor of ras and strarigin genes showed reduced level of its transcription compared to untreated U-937 cell. The significant change of level of transcription was not found in well-known ionizing radiation(IR)-responsive gene, such as transcription factor TP53 and p53 related gene, except ataxia telangiectasia mutated gene.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2019년도 춘계학술발표대회
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• pp.23-25
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• 2019

낸드 플래시 메모리(NAND Flash Memory)는 컴퓨터 시스템의 대용량 저장장치를 위한 소자로써, 대용량화의 주요 원인으로는 메모리 셀(Cell) 당 저장할 수 있는 비트 수를 증가시킴으로써 집적도를 증가시킨 것이다. 그러나, 이러한 집적도의 증가는 에러의 증가를 가져와서 저장장치에서 가장 중요한 신뢰성이 급격하게 저하하는 요인이며, 저장장치의 생명주기(Lifetime)을 감소시키게 된다. 기존에 낸드 플래시 메모리 저장장치의 Lifetime을 증대시키기 위해서 P/E cycle을 고려하여 데이터 영역의 일부를 점점 더 ECC 영역으로 변경시키는 방식을 적용한 바가 있다. 이러한 방식은 데이터 영역의 감소로 인한 저장장치 내에서 관리되는 호스트-플래시 간 데이터 관리 크기의 미스매치로 인한 여러 가지 오버 헤드를 생성한다. 본 연구에서는 P/E cycle에 따른 데이터 영역의 ECC 영역으로의 전환을 통한 Lifetime을 증가시키는 방식에 있어서, 오버헤드를 줄이기 위한 캐쉬 관리 구조 및 매핑 관리 구조에 대한 설계를 진행하였다. 이러한 설계를 낸드 플래시 메모리 기반 저장장치에 적용할 경우, LifeTime을 증대시키기 위해서 ECC를 데이터 영역으로 확장하는 방식을 사용할 때 저하될 수 있는 일반 읽기 및 쓰기의 성능 저하를 어느 정도 감소시켜줄 수 있을 것으로 기대한다.