• Title/Summary/Keyword: cdk

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Anti-proliferative Effects of the Isothiocyanate Sulforaphane on the Growth of Human Cervical Carcinoma HeLa Cells (Sulforaphane에 의한 HeLa 인체자궁경부함세포의 증식 억제 기전 연구)

  • Park Soung Young;Bae Song-Ja;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.397-405
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    • 2005
  • Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human cancer cells, however its molecular mechanisms are poorly understood. In the present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human cervical carcinoma HeLa cells. Treatment of HeLa cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells (9.83 fold of control). This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of cyclin A and cyclin-dependent kinase (Cdk)4 protein and concomitant induction of Cdc2, Cdk inhibitor p16 and p21. However, sulforaphane did not affect the levels of cyelooxygenases and telomere-regulatory gene products. Although further studies are needed, the present work suggests that sulforaphane may be a potential chemoprevetive/ chemotherapeutic agent for the treatment of human cancer cells.

Role of Iridin Isolated from Iris koreana Nakai on Doxorubicin-induced Necrosis in HK-2 Cells, and Effect on Cancer Cells (노랑붓꽃에서 분리된 Iridin의 독소루비신 유도 HK-2 세포 괴사에 대한 역할 및 암세포에 대한 작용)

  • Nho, Jong Hyun;Lee, Ki Ho;Jung, Ho Kyung;Lee, Mu Jin;Jang, Ji Hun;Sim, Mi Ok;Jung, Ja Kyun;Jung, Da Eun;Cho, Hyun Woo
    • Korean Journal of Plant Resources
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    • v.31 no.2
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    • pp.95-101
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    • 2018
  • Doxorubicin is a anti-cancer drugs that interferes with the growth and spread of cancer cells in human body. Doxorubicin is used to treat different types of cancers that affect the ovary, thyoid and lungs, but induced side effect such as nephrotoxicity and cardiotoxicity. Thus, we investigated that the effect of iridin on doxorubicin-induced necrosis in HK-2 cells, a human proximal tubule cell. To confirm effect of iridin on doxorubicin-induced necrosis, HK-2 cells are treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ iridin. $80{\mu}M$ iridin reduced $10{\mu}M$ doxorubicin-induced necrosis, the mitochondrial over activation and caspase-3 activation. However, iridin reduces anti-cancer effect of doxorubicin such as PARP1 and caspase-3 activation, checkpoint proteins (CDK4 and CDK6) in NCI-H1129 cells (Human non-small cell lung cancer cell). In HCT-116 cells (Human colorectan cancer cell), iridin do not increased protein expression of CDK4 and CDK6 decreased by doxorubicin. Results indicate that treatment of iridin was diminished doxorubicin-induced necrosis in HK-2 cells. However, iridin was decreased anti-cancer effect of doxorubicin on NCI-H1229, but not HCT-116. Thus, further experiment are required to iridin treatment on various cancer cells and animal models because effect of iridin different cell type.

Induction of Cell Cycle Arrest at G2/M phase by Ethanol Extract of Scutellaria baicalensis in Human Renal Cell Carcinoma Caki-1 Cells (황금 에탄올 추출물에 의한 인간 신장암 세포주 Caki-1의 G2/M arrest 유발)

  • Park, Dong-Il;Jeong, Jin-Woo;Park, Cheol;Hong, Su-Hyun;Shin, Soon-Shik;Choi, Sung-Hyun;Choi, Yung-Hyun
    • Herbal Formula Science
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    • v.23 no.2
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    • pp.199-208
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    • 2015
  • Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

Effects of Sophorae Radix Extracts on the Expression ofcell cycle regulatory porteins in Human Gingival Fibroblasts (고삼추출물이 치은섬유아세포의 세포주기 조절단백질 발현에 미치는 영향)

  • Kim, Heung-Sik;Kim, Hyun-A;Yu, Yong-Ouk;Kang, Tai-Hyun;Kim, Youn-Chul;Kim, Tak;Pee, Sung-Hee;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.30 no.4
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    • pp.869-885
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    • 2000
  • Fibroblasts are major cellular components of gingiva and periodontal ligament. They regulate the healing process after surgery or injury. Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Sophorae radix have been traditionally used as an anti-bacterial and antiinflammatory drug in oriental medicine. The purpose of present study was to investigate the effects of Sophorae radix extract on cell cycle progression and its molecular mechanism in human gingival fibroblasts. Sophorae radix extracts($100{\mu}g/ml$) notably increased cell proliferation and cell activity in the human gingival fibroblasts as compared to non-supplemented controls. There was an increase in the S phase and a decrease in the G1 phase in $100{\mu}g/ml$ of Sophorae radix extracts group as compared to non-supplemented controls. The level of cyclin E and cdk 2 protein in test group was higher than that of control groups. But that of cyclin D, cdk 4, and cdk 6 was not distinguished from controls. The level of p53 protein in test group was lower than that of controls, whereas that of p21 was not different. The level of pRB protein in test group was higher than that of controls, whereas that of p16 was lower. These results indicate that the increase of cell proliferation by Sophorae radix extracts may be due to the increased expression of cyclin E and cdk 2, and the decreased expression of p53 and p16 in human gingival fibroblasts.

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Regulation of Cyclin D3 by Calpain Protease in Human Breast Carcinoma MDA-MB-231 Cells (인체 유방암세포에서 calpain protease에 의한 cyclin D3의 발현 조절)

  • Choi, Byung-Tae;Kim, Gun-Do;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.16 no.4
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    • pp.598-604
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    • 2006
  • The $Ca^{2+}-activated$ neutral protease calpain induced proteolysis has been suggested to play a role in certain cell growth regulatory proteins. Cyclin proteolysis is essential for cell cycle progression. D-type cyclins, which form an assembly with cyclin-dependent kinases (cdk4 and cdk6), are synthesized earlier in G1 of the cell cycle and seem to be induced in response to external signals that promote entry into the cell cycle. Here we show that cyclin D3 protein levels are regulated at the posttranscriptional level by calpain protease. Treatment of human breast carcinoma MDA-MB-231 cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. The specific inhibitor of the 26S proteasome, lactacystin, the lysosome inhibitors, ammonium chloride and chloroquine, and the serine protease inhibitor, phenylmethylsulfonylfluoride (PMSF), did not block the degradation of cyclin D3 by lovastatin and actinomycin D. Results of in vitro degradation of cyclin D3 by purified calpain showed that cyclin D3 protein is degraded in a $Ca^{2+}-dependent$ manner, and the half-life of cyclin D3 protein was dramatically increased in LLnL treated cells. These data suggested that cyclin D3 protein is regulated by the $Ca^{2+}-activated$ protease calpain.

Effects of Pear Extracts Cultured Under Conventional and Environment-friendly Conditions on Cell Proliferation in Rat Hepatocytes (친환경 배 및 관행재배 배 추출물이 간세포 성장에 미치는 효과)

  • Yoon, Byung-Chul;Kim, Kil-Yong;Park, Soo-Hyun
    • Applied Biological Chemistry
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    • v.49 no.3
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    • pp.233-237
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    • 2006
  • In the present study, we compared the functional analysis of pear extracts cultured in conventional and environment-friendly conditions in primary cultured rat hepatocytes. ATP synthesis significantly increased by the treatment with environment friendly cultured pear powder but not by conventional group. In addition, cell proliferation using $[^3H]$-thymidine incorporation was also stimulated by environment-friendly cultured pear extract compared to conventional group. Moreover, the expressions of CDK-2 and CDK-4 were increased but p21WAF1/Cip1 and p27 Kip1 decreased by environment-friendly cultured pear extract but not by conventional group. In conclusion, environment-friendly cultured pear powder has stimulatory effect on cell proliferation compared to conventional group in primary cultured rat hepatocytes.

P25: A hidden target for AD therapeutic.

  • Ha, Il-Ho
    • 한국약용작물학회:학술대회논문집
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    • 2006.04a
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    • pp.93-105
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    • 2006
  • P25/CDK5 phosphorylates BACE1. 2. P25 is a new target for AD therapeutics. 3. P25 inhibitors should block both $A{\beta}$ pathway and Tau pathway.

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