• Journal of Life Science
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• v.23 no.6
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• pp.832-837
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• 2013

In this study, it was investigated the possible mechanisms by which glutamine deprivation exerts its anti-proliferative action in cultured human prostate carcinoma PC3 cells. Glutamine deprivation resulted in inhibition of growth and G2/M arrest of the cell cycle in a time-dependent manner without apoptosis induction, as determined by MTT assay, DAPI staining and flow cytometry analyses. The induction of G2/M arrest by glutamine deprivation was associated with the inhibition of expression of Cdc2, cyclin A and cyclin B1, and up-regulation of the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) in both transcriptional and translational levels. Moreover, glutamine deprivation increased the phosphorylation of checkpoint kinase (Chk)1 and Chk2; however, the levels of Cdc25C phosphorylation were decreased in response to glutamine deprivation in a time-dependent manner. Our data provide a first biochemical evidence that glutamine deprivation suppresses cell viability through G2/M phase arrest without induction of apoptosis in PC3 cells.

• Journal of the Korean earth science society
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• v.27 no.4
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• pp.390-400
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• 2006

The purpose of this study is to propose an improvement plan based on an analysis of the current earth science teacher education curriculum in the department of education in the four fields of teaching profession theory: student-teacher practice, subject lesson education, and subject content education. The following are the conclusions and suggestions of this study. In case of teaching profession theory, too much emphasis is put on pedagogical theory over practical issues, and a problem arises upon completion. Therefore, it is sugguest that teaching profession theory might be completed before subject lesson education to ensure more authentic subjects performing teaching profession. The current term for student-teacher training is too short to understand the whole school system. Current school system does not have any off-job training course or internship system. Therefore, student-teacher training term should be increased by at least $3{\sim}6$ months to play a vital role in the current system. The credit number of subject lesson education is too small compared with subject content education. Consequently, the credit number of subject lesson education should be increased, and more professor majored in subject lesson education should be recruited. Significant deviation between the content of subject content education and that of middle school grade exists, and there is also much difference in the ratio of subject according to university. To get rid of these problems, subject content education should be connected with subject lesson education and appropriate number of credit needs to be assigned to each subject domain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.900-907
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• 2004

The antiproliferative effect of the water extract of the branch and root bark of Ulmi Pumilae Cortex(WEUPC) was investigated on the p53-negative human leukemia cell line (HL-60). A dose- and time-dependent inhibition of cell growth was observed; this effect appears to be due to induction of apoptosis. Involvement of oxidative stress is indicated by a dose-dependent increase in intracellular reactive oxygen species levels. In addition. anti-apoptic effect was observed in the cells simultaneously treated with WEUPC and the anti-oxidant N-acetylcysteine. WEUPC did not affect the anti-apoptotic Bcl-2 and the pro-apoptotic Bax, whereas p21/sup WAF1/CIPl/ was enhanced in a dose- and time-dependent fashion; this effect was partially inhibited by N-acetylcysteine. The increase in p21/sup WAF1/CIPl/ was accompanied by a parallel accumulation of cells in the G1 phase of the cycle. These results suggest that the p53-independent induction of p21/sup WAF1/CIP/ and the induction of apoptosis may mediate the anti proliferative effect of WEUPC at least in this study; on the basis of this observation, WEUPC could be proposed as an useful adjunct to the treatment of p53-deficient tumors, which are often refractory to standard chemotherapy.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.70-77
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• 1999

Purpose : The expression of p53, P211WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. Materials and Methods Mammary adenocarcinoma cells of hi) mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After Incubation at 37Microbioiogy, College of Medicine Dong A University for 0$\~$48 h, the extort of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, p211WAFfCIP, Bcl-2, and Bu protein levels. Results : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2IM arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH 6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. Bcl-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. Conclusions : The molecular mechanism underlying radiation-induced apoptosis in dinerent pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and P211YVAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2iM arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of Bcl-2 family was unclear in SCK mammary adenocarcinoma cell line.

• Journal of Life Science
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• v.24 no.1
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• pp.92-97
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• 2014

Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

• 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.31 no.4
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• pp.400-409
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• 2021

Sanguinarine, a natural benzophenanthridine alkaloid, has been considered a potential therapeutic target for the treatment of cancer because it can induce apoptosis in human cancer cells; however, the underlying mechanisms of action still remain unclear. Tumor suppressor p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to anticancer agents. Therefore, in the present study, the role of p53 during apoptosis induced by sanguinarine was investigated in p53wild type (WT, p53+/+) and p53null (p53+/+) HCT116 colon carcinoma cells. Sanguinarine significantly caused greater reductions in cell viability in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells. Consistently, sanguinarine promoted more DNA damage and apoptosis in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells while increasing the expression of p53 and cyclin-dependent kinase inhibitor p21^WAF1/CIP1. Sanguinarine increased the activity of caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and it activated caspase-3, a typical effect caspase, in HCT116 (p53+/+) cells. Sanguinarine also increased the generation of reactive oxygen species (ROS), and the Bax/Bcl-2 ratio, while destroying the integrity of mitochondria in HCT116 (p53+/+) cells, but not in HCT116 (p53-/-) cells. Overall, the results indicate that sanguinarine induced p53-dependent apoptosis through ROS-mediated activation of extrinsic and intrinsic apoptotic pathways in HCT116 colorectal cancer cells.

• Journal of Microbiology and Biotechnology
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• v.14 no.5
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• pp.978-984
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• 2004

In the course of screening for a novel inhibitor of CDC2, HY558-1 was isolated from a culture broth of Penicillium minioluteum F558. Moreover, it was found that HY558-1 had an effect on both the cell cycle regulation and apoptosis of human cervical adenocarcinoma HeLa cells. A flow cytometric analysis of HeLa cells revealed appreciable cell cycle arrest at the G1 and G2/M phases following treatment with HY558-1. Furthermore, DNA fragmentation due to apoptosis was observed in HeLa cells treated with HY558-1. To obtain further information on the cell cycle arrest and apoptotic induction induced by HY558-1, the expression of certain cell cycle and apoptosis-associated proteins was examined using a Western blot analysis. The results revealed that HY558-1 inhibited the phosphorylation of pRb and decreased the expression levels of CDK2, CDC2, and cyclin A in the cell cycle progression. It was also shown that the level of $p21^{WAF1/CIP1}$ was increased in HeLa cells treated with 0.52 mM of HY558-1. Accordingly, HY558-1 was found to inhibit the proliferation of HeLa cells through the induction of G1 phase arrest by inhibiting pRb phosphorylation via an upregulation of $p21^{WAF1/CIP1}$, and G2/M phase arrest by directly inhibiting CDC2 and cyclin A. Moreover, HeLa cells treated with 0.52 mM of HY558-1 exhibited apoptotic induction associated with the cleavage of Bid and release of cytochrome c from mitochondria into the cytosol. Subsequent investigation of the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP) suggested that the mitochondrial pathway was primarily involved in the HY558-1-induced apoptosis in HeLa cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1449-1455
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• 2004

Bufonis venenum (dried toad venom; Chinese name, Chan su) is a traditional Chinese medicine obtained from the skin venom gland of the toad. It has long been used in treating arrhythmia and other heart diseases in China and other Asian countries. Additionally, Bufonis venenum has been reported to selectively inhibit the growth of various lines of human cancer cells. In the present study, it was examined the effects of extract of Bufonis venenum (EBV) on the growth of human bladder carcinoma cell line T24 in order to investigate the anti-proliferative mechanism and induction of apoptosis by EBV. Treatment of T24 cells to EBV resulted in the growth inhibition, morphological change and induction of apoptotic cell death in a dose-dependent manner. Flow cytometric analysis revealed that EBV treatment caused G2/M phase arrest of the cell cycle and down-regulation of cyclin A, cyclin B1 and Cdc2, which was associated with a marked up-regulation of cyclin-dependent kinases (Cdks) inhibitor p21 (WAF1/CIP1) in a p53-independent manner. The Cdc25C expression was also significantly inhibited by EBV treatment, however Wee1 kinase expression was not affected. The induction of apoptotic cell death by EBV was connected with down-regulation of anti-apoptotic Bcl-XS/L expression without alteration pro-apoptotic Bax expression. Taken together, these findings suggest that EBV may be a potential chemotherapeutic agent for the control of human bladder carcinorma cells and further studies will be needed to identify the active compounds that confer the anti-cancer activity of EBV.

• 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.