• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.114-114
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• 2003

p53 has identified as a tumor suppressor protein to protect cells from DNA damage. p53, also well known for a transcription factor, can activate genes such as p21, bax, gadd45 and induce a number of the responses such as differentiation, senescence, DNA repair, apoptosis and the inhibition of angiogenesis to protect cells. Many mechanisms of p53 activation have been studied.(omitted)

• Animal cells and systems
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• v.13 no.4
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• pp.399-403
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• 2009

$p19^{ras}$ is an alternative splicing variant of the proto-oncogene c-H-ras pre-mRNA of $p21^{ras}$. In contrast to $p21^{ras}$, $p19^{ras}$ does not have a C-terminal CAAX motif that targets the plasma membrane and is localized to both the cytoplasm and nucleus. We found that $p19^{ras}$ activated the transcriptional activity of $p73{\beta}$ through protein-protein interactions in the nucleus. p73 is known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homologue of p53, p73-mediated apoptosis has not yet been clearly elucidated. In this study, we demonstrate that the interaction between $p19^{ras}$ and $p73{\beta}$ accelerated $p73{\beta}$-induced apoptosis through a caspase-3 dependent pathway. Treatment with DEVD-CHO, a caspase inhibitor, also strengthened $p73{\beta}$-mediated apoptosis through a caspase-3 dependent pathway. Furthermore, the enhanced transcriptional activity of endogenous $p73{\beta}$ by treatment with Taxol was amplified by $p19^{ras}$ overexpression, which markedly increased caspase-3 dependent apoptosis in the p53-null SAOS2 cancer cell line. Our findings indicate a functional linkage between $p19^{ras}$ and p73 in caspase-3 mediated apoptosis of cancer cells.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.309-314
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• 2016

We first demonstrated that cordycepin inhibited cell growth and triggered apoptosis in U87MG cells with wild-type p53, but not in T98G cells with mutant-type p53. Western blot data revealed that the levels of procaspase-8, -3, and Bcl-2 were downregulated in cordycepin-treated U87MG cells, whereas the levels of Fas, FasL, Bak, cleaved caspase-3, -8, and cleaved PARP were upregulated, indicating that cordycepin induces apoptosis by activating the death receptor-mediated pathway in U87MG cells. Cordycepin-induced apoptosis could be suppressed by only SB203580, a p38 MAPK-specific inhibitor. These results suggest that cordycepin triggered apoptosis in U87MG cells through p38 MAPK activation and inhibition of the Akt survival pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.417-425
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• 2017

Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

• The Journal of Natural Sciences
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• v.9 no.1
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• pp.31-37
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• 1997

Apoptosis is an important event in the anticancer drug therapy. p53 was demonstrated to serve a key component to lead tumor cell death by inducing apoptosis. However, recent study showed the presence of p53 independent apoptotic pathway (Gaftenhaus et al., 1996). We were curious to know it apoptosis induced by adriamycin, a genotoxic anticancer agent, involved p53 gene mutation. Thus this study investigated the p53 gene mutation status among HeLa cell population during apoptosis induced by adriamycin. Under our experimental condition, 12 hour treatment of 1 ${\mu}m$ adriamycin caused apoptosis which was monitored by DNA fragmentation assay. In order to see the p53 gene mutation status, exons of 5, 7 and 8 of p53 gene, where previously reported p53 mutation hot spots reside, were amplified by PCR and nucleotide sequence change was scanned. However, no nucleotide change was observed among apoptotic HeLa cell population. Therefore this study demonstrated that adriamycin induced apoptosis without causing p53 gene damage.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9791-9795
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• 2014

To study the gene expression change and possible signal pathway during androgen-dependent prostate cancer (ADPC) becoming androgen-independent prostate cancer (AIPC), an LNCaP cell model of AIPC was established using flutamide in combination with androgen-free environment inducement, and differential expression genes were screened by microarray. Then the biological process, molecular function and KEGG pathway of differential expression genes are analyzed by Molecule Annotation System (MAS). By comparison of 12,207 expression genes, 347 expression genes were acquired, of which 156 were up-ragulated and 191 down-regulated. After analyzing the biological process and molecule function of differential expression genes, these genes are found to play crucial roles in cell proliferation, differntiation, cell cycle control, protein metabolism and modification and other biological process, serve as signal molecules, enzymes, peptide hormones, cytokines, cytoskeletal proteins and adhesion molecules. The analysis of KEGG show that the relevant genes of AIPC transformation participate in glutathione metabolism, cell cycle, P53 signal pathway, cytochrome P450 metabolism, Hedgehog signal pathway, MAPK signal pathway, adipocytokines signal pathway, PPAR signal pathway, TGF-${\beta}$ signal pathway and JAK-STAT signal pathway. In conclusion, during the process of ADPC becoming AIPC, it is not only one specific gene or pathway, but multiple genes and pathways that change. The findings above lay the foundation for study of AIPC mechanism and development of AIPC targeting drugs.

• Herbal Formula Science
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• v.30 no.3
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• pp.175-182
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• 2022

Objective : This study aims to investigate the active ingredients and potential mechanisms of the beneficial herb on human cancers such as the liver by employing network pharmacology. Methods : Ingredients and their target information was obtained from various databases such as TM-MC, TTD, and Drugbank. Related protein for liver cancer was retrieved from the Comparative Toxicogenomics Database and literature. A hypergeometric test and gene set enrichment analysis were conducted to evaluate associations between protein targets of red ginseng (Panax ginseng C. A. Meyer) and liver cancer-related proteins and identify related signaling pathways, respectively. Network proximity was employed to identify active ingredients of red ginseng on liver cancer. Results : A compound-target network of red ginseng was constructed, which consisted of 363 edges between 53 ingredients and 121 protein targets. MAPK signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, TGF-beta signaling pathway, and cell cycle pathway was significantly associated with protein targets of red ginseng. Network proximity results indicated that Ginsenoside Rg1, Acetic Acid, Ginsenoside Rh2, 20(R)-Ginsenoside Rg3, Notoginsenoside R1, Ginsenoside Rk1, 2-Methylfuran, Hexanal, Ginsenoside Rd, Ginsenoside Rh1 could be active ingredients of red ginseng against liver cancer. Conclusion : This study suggests that network-based approaches could be useful to explore potential mechanisms and active ingredients of red ginseng for liver cancer.

• Bulletin of the Korean Mathematical Society
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• v.53 no.1
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• pp.181-193
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• 2016

During the past two decades or so, fractional integral inequalities have proved to be one of the most powerful and far-reaching tools for the development of many branches of pure and applied mathematics. Very recently, many authors have presented some generalized inequalities involving the fractional integral operators. Here, using the pathway fractional integral operator, we give some presumably new and potentially useful fractional integral inequalities whose special cases are shown to yield corresponding inequalities associated with Riemann-Liouville type fractional integral operators. Relevant connections of the results presented here with those earlier ones are also pointed out.

• Journal of Life Science
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• v.26 no.8
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• pp.887-894
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• 2016

The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3959-3963
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• 2014

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.