• Title/Summary/Keyword: CDK10

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Piceatannol-Induced G1 Arrest of the Cell Cycle is Associated with Inhibition of Prostaglandin E2 Production in Human Gastric Cancer AGS Cells (Piceatannol에 의한 AGS 인체 위암세포의 G1 Arrest 및 Prostaglandin E2 생성의 억제)

  • Choi, Yung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.7
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    • pp.907-913
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    • 2012
  • Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

Induction of Selective Cell Death of Oral Squamous Carcinoma Cells by Integrin α2 Antibody and EGFR Antibody (인테그린 α2와 상피성장인자수용체 차단항체의 저해작용을 통한 구강편평상피암 세포의 선택적 제거)

  • Choi, Yeon-Sik;Kim, Gyoo-Cheon;Yoon, Sik;Hwang, Dae-Seok;Kim, Cheol-Hun;Jeon, Young-Chan;Byun, June-Ho;Shin, Sang-Hun;Kim, Uk-Kyu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.3
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    • pp.143-154
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    • 2013
  • Purpose: This study was to find efficacy of integrin alpha2 (${\alpha}_2$) and epidermal growth factor receptor (EGFR) as tumor marker of oral squamous cell carcinoma (SCC) and clarify the selective cell death effect of anti-integrin ${\alpha}_2$ and anti-EGFR on SCC cells, additionally testify conjugated gold nanoparticles (GNP) with air plasma for selective cell death of oral SCC. Methods: Expression of integrin ${\alpha}_2$, EGFR on human SCC cells (SCC25) were examined by western blot. SCC25 cells were treated with anti-integrin ${\alpha}_2$, anti-EGFR and analysed by Hemacolor staining, immunoflorescence staining, FACS flow cytometry. Conjugated GNP with integrin ${\alpha}_2$, EGFR antibody were treated by air plasma on SCC cells. Results: Integrin ${\alpha}_2$ and EGFR were over-expressed on SCC25 cells than normal lung WI-38 cells. The cell viability rate of SCC25 cells treated with anti-integrin ${\alpha}_2$, anti-EGFR was lower than WI-38 cells. The concentration changes of nucleus, releasing cytochrome c and apoptosis inducing factor (AIF) from mitochondria to cytosol were observed. The changes of proteins related with apoptosis were observed. Increase of bax, bcl-xL, activation of caspase-3, -7, -9, and fragmentation of PARP, DFF45 and decrease of lamin A/C in SCC25 cells were observed. In FACS, increase of sub-$G_1$ and S phase was observed. Cell cycle related proteins, Such as cyclin D1, cyclin dependent kinase (CDK) 4, cyclin A, cyclin E, CDK 2, p27 were decreased. After SCC25 cells treated with conjugatged GNP-Integrin ${\alpha}_2$, GNP-EGFR, additionally air plasma, the cell death rate was significantly increased. Conclusion: Integrin ${\alpha}_2$, EGFR were over-expressed in oral SCC cells. Anti-integrin ${\alpha}_2$, anti-EGFR in SCC25 cells induced apoptosis selectively. When GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR were treated with air plasma on SCC25 cells, cancer cells were died more selectively. GNP-anti integrin ${\alpha}_2$, GNP-anti EGFR with air plasma could be treatment choice of oral SCC.

Anti-oxidant, Anti-inflammatory and Anti-cancer Effect of Methanol Extract of Pogostemon cablin (광곽향 메탄올 추출물의 항산화, 항염증 및 암세포 증식 억제 효과)

  • Yun, Seung Geun;Jin, Soojung;Jeong, Hyun Young;Yun, Hee Jung;Do, Mi young;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.25 no.1
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    • pp.44-52
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    • 2015
  • In the present study, the substance that show anti-proliferation of cancer cells as well as anti-oxidant and anti-inflammatory effect was searched. As a results, the methanol extract of Pogostemon cablin (P. cablin), is a well-known herb for traditional medicine in Korea and China for treating the digestive disorders, less of appetite, vomiting and diarrhea, inhibited the growth of various cancer cells such as A549, HepG2, MCF7 and HT29 cells. Cytotoxic effect of methanol extraction of P. cablin was excellent in A549 cells. P. cablin extract induced cell cycle arrest at G1 phase of A549 in a dose dependent manner. And it induced phosphorylation of p38 and Cdc25A and reduced expression of Cdc25A, Cdks, Cyclins and phospho-Retinoblastoma (Rb) proteins. Therefore, P. cablin extract seems to act through the p38 - Cdc25A - Cdk - Cyclin - Rb pathway in A549 cells. In addition, P. cablin extract showed anti-oxidant effect by DPPH free radical scavenging assay and anti-inflammation effect by inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) in RAW 264.7 cells in a dose-dependent manner. Taken together, these results suggest that P. cablin may be used as not only candidate materials for anti-cancer, anti-inflammatory and anti-oxidant, moreover, it would be possible utilized in various health functional food materials.

Growth Inhibition of Human Hepatoma and Bladder Carcinoma Cells by DNA Topoisomerae Inhibitor β-lapachone (DNA topoisomerase 억제제인 β-lapachone에 의한 인체 간암 및 방광암세포 증식억제에 관한 연구)

  • Choi Da Yean;Lee Jae Il;Chung Hyun Sup;Seo Han Gyeol;Woo Hyun Joo;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.323-331
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    • 2005
  • The objective of the present study was to investigate the effect of $\beta-lapachone$, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America, on the cell growth of human hepatoma (HepG2) and bladder (T24) carcinoma cells. Exposure of cancer cells to $\beta-lapachone$ resulted in growth inhibition, morphological changes and apoptosis in a concentration-dependent manner, which could be proved by MTT assay and flow cytometry analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that $\beta-lapachone$ did not affect the levels of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAFl/CIPl) expression. However, the transcriptional factor Sp-l and proliferating cell nuclear antigen (PCNA) protein levels were significantly down-regulated by $\beta-lapachone$ in both cell lines. Moreover, $\beta-lapachone$ treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-l (TEP-l). Taken together, these findings suggest that $\beta-lapachone$-induced inhibition of human hepatoma and bladder carcinoma cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and provide important new insights into the additional mechanisms of the anti-cancer activity of $\beta-lapachone$.

Silibinin Inhibits Cell Growth and Induces Apoptosis through Cell-cycle Arrest in PC-3 Prostate Cancer Cells (인간 전립선 암세포 PC-3 세포에서 Silibinin의 세포주기조절을 통한 세포사멸 유도 효과)

  • Kim, Sang-Hun;Kim, Kwang-Youn;Yu, Sun-Nyoung;Jeon, Hyun-Joo;Jin, Young-Rang;Lee, Chang-Min;Ahn, Soon-Cheol
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1573-1578
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    • 2011
  • Milk thistle (silybum marianum) is a famous dietary supplement widely used in the United States and Europe. Silbinin is a major biologically active compound of milk thistle and has strong antioxidant and radical scavenger activities. Anticancer activities, as well as chemopreventive effects on various cancer cell lines, including prostate, lung, colon, skin, and bladder, have also been reported in silbinin. In the present study, we investigated the anticancer effects of silibinin and apoptosis through cell cycle arrest on prostate cancer cell PC-3. We performed cell viability by MTT assay and western blotting to confirm cell cycle check point proteins such as cyclin A/D1/E and cyclin-dependent kinase (CDK) 2/4/6. To quantify silibinin-induced apoptotic cell death of PC-3, Annexin V and PI double staining was performed by flow cytometry, by which its cell distribution was determined. As a result, silibinin inhibited the cell growth of PC-3 cells in a time- and dose-dependent manner, and its treatment resulted in cell cycle arrest at the G1 phase. Also the level of cell cycle check point proteins (cyclin, CDK) was decreased by silibinin in a dose-dependent manner. Taken together, we suggest that apoptosis of prostate cancer cell line PC-3 induced by silibinin is associated with cell cycle arrest through decrease of cell cycle check point proteins, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage.

Induction of Mitotic Arrest and Apoptosis by Diallyl Trisulfide in U937 Human Leukemia Cells (U937 인체혈구암세포에서 diallyl trisulfide에 의한 mitotic arrest와 apoptosis 유발)

  • Park, Hyun Soo;Lee, Jun Hyuk;Son, Byoung Yil;Choi, Byung Tae;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.5
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    • pp.622-628
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    • 2013
  • Diallyl trisulfide (DATS), one of the major organosulfur components of garlic (Allium sativum), has various biological effects such as anti-microbial and anti-cancer activities. However, the molecular mechanisms of growth inhibition related to cell cycle arrest are poorly understood. In this study, we investigated the effects of DATS on cell cycle progression in U937 human leukemia cells. Treatment with DATS in U937 cells resulted in inhibition of cell viability through G2/M arrest and apoptosis. DATS-induced G2/M arrest was associated with up-regulation of cyclin B1 and cyclin-dependent kinase 1 (CDK1). DATS also significantly increased levels of phospho-histone H3, which is a mitosis-specific marker, indicating that DATS induced mitotic arrest but not G2 arrest in U937 cells. DATS treatment also generated the reactive oxygen species (ROS) in U937 cells; however, pretreatment with N-acetyl-l-cysteine (NAC), a ROS scavenger, significantly attenuated DATS-induced mitotic arrest and apoptosis. Taken together, our data indicate that DATS exhibits anti-cancer effects through mitotic arrest and apoptosis in a ROS-dependent manner.

Effects of Cyclosporin A on the Cell Cycle Regulation of Human Gingival Fibroblasts (Cyclosporin A가 치은섬유아세포의 세포주기조절에 미치는 영향)

  • Pi, Sung-Hee;Kim, Dae-kyum;Kim, Tak;You, Yong-Ouk;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.31 no.3
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    • pp.611-623
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    • 2001
  • Cyclosporin A is a cyclic polypeptide produced by the metabolism of fungi. It is widely used at present as immunosuppressive treatment following organ transplants. It is also used to deal with autoimmune diseases such as rheumatoid arthritis or type II diabetes. Gingival hyperplasia is one of the most frequent side-effects associated with the prescription of Cyclosporin A. The mechanisms involved in Cyclosporin A induced gingival hyperplasia are not yet clear. In vitro Cyclosporin A promotes proliferation of gingival fibroblasts, that Cyclosporin A act as a mitogen. Its action is based on mitosis of gingival fibroblasts regulated by cell cycle regulatory proteins. It was the purpose of the present study to examine the effects of Cyclosporin A on human gingival fibroblasts by means of biological and biochemical criteria. In this present study, we examined change of cell proliferation, cell activity, cell viability and cell cycle progression after application of Cyclosporin A. We also examined expression of cell cycle regulatory proteins by western blot analysis. Human gingival fibroblasts were cultured for 48 hours with application of Cyclosporin A at concentrations of 0.01, 0.1, 1, and 10 ng/ml. Cyclosporin A(1 ng/ml) significantly increased the cell activity of gingival fibroblast. Proliferation and viability of gingival fibroblasts were also increased in group treated with 1 ng/ml of Cyclosporin A compared to control group. In the cell cycle analysis, S phase was increased and G1 phase was decreased in the group treated with 1 ng/ml of Cyclosporin A. Cyclosporin A increased the expression of cdk4 and inhibited the expression of pRB and p21. These results suggest that 1 ng/ml of Cyclosporin A may increase the cell cycle progression of human gingival fibroblasts, and its mechanisms may increase the expression of cdk4 and decrease the expression of pRB and p21.

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Study on the Demand Characteristics of Epoxy Resins Applied to the Restoration of Ceramics (도자기 복원에 사용되는 에폭시계 고분자수지의 요구 특성 연구)

  • Nam, Byeongjik;Jeong, Seri;Jang, Sungyoon
    • Journal of Adhesion and Interface
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    • v.13 no.4
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    • pp.171-181
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    • 2012
  • The demand characteristics of the conventional 12 kinds of epoxy resins which have been used for restoration of the ceramic relics were investigated to provide standards of the effective materials in this study. The result of durability analysis showed that a liquid type is more effective in ceramic relics (low damage, high strength), and a paste type is more effective in earthenware relics (high damage, low strength). The result of workability analysis appears that the liquid type is higher than the paste type, and a slow curing type is higher than a fast curing type in surface hardness. Therefore, in the case of the liquid type which is hard to reprocess due to high surface hardness, it is necessary to conduct a study on improving physical properties by adding filler. The result of the gloss analysis on epoxy resins showed that the liquid type (colorless) has higher gloss than the paste type, and the slow curing type has higher gloss than the fast curing type in liquid types. CDK-520A/520B and Araldite SV 427-2/HV 427-1 showed the most similar gloss to $700^{\circ}C$ earthenware, Devcon 5 minute, EPO-TEK 301-2, and Quik Wood showed the most similar gloss to celadon and whiteware, Quik Wood, EPO-TEK 301-2, and Devcon 5 minute showed the most similar gloss to buncheongware. It is necessary for conservator to decide the range of the restoration surface by predicting the increase and decrease of the restoration surface because most of the epoxy resins caused the volume change in curing process.

A Study on Conservation and Manufacturing Techniques of a Seated Avalokiteshvara with a Thousand Hands of Goryeo Dynasty (고려시대 금동제십일면천수관음보살좌상의 보존처리 및 제작기술 연구)

  • Gwak, Hong In;Kwon, Mi Hye
    • Journal of Conservation Science
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    • v.35 no.3
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    • pp.253-258
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    • 2019
  • The gilt bronze statue, Seated Avalokiteshvara with a Thousand Hands, of the Goryeo dynasty, is the only one in Korea of its kind that has undergone a conservation process for the special exhibition entitled GORYEO: The Glory of Korea. For the conservation treatment, first, a component analysis (XRF) was conducted, and a manufacturing technique (CT) was analyzed. The results of the investigation revealed that the statue was alloyed with Cu, Sn, and Pb ternary bronze. Its surface, except for the detached plating layers, was originally plated using the mercury amalgam method. This statue was assembled after separately casting each part of the body, such as the left and right arms and the wrists, including the hands, with objects. In particular, each wrist was cast and fitted with a metal nail to express each object in the hands more precisely. Inside the statue, there were five iron cores: two for the head, one for the left elbow, one for the right flank, and one for the right waist. For the preservative treatment, natural adhesive agents, including vegetable gelatin and glue (20%), were mixed with alcohol to protect the base metal and adhere to the plating layers. Using synthetic resin (CDK 520+SN-sheet) for the damaged parts, the restored parts could be attached and detached to/from the statue. Eventually, the compositional analysis and conservation treatment left the statue in a stable condition and ready for exhibitions and future studies.

Effects of an Anti-cancer Drug, Tubastatin A, on the Growth and Development of Immature Oocytes in Mice (항암제 tubastatin A에 의한 생쥐 미성숙 난모세포의 성장과 발달에 미치는 효과)

  • Choi, Yun-Jung;Min, Gyesik
    • Journal of Life Science
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    • v.29 no.1
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    • pp.105-111
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    • 2019
  • In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.