• Title/Summary/Keyword: cyclin D

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Effects of Cervi Parvum Cornu on Cell Cycle Regulation in Human Fetal Osteoblasts (녹용이 사람 태아 골모세포의 세포주기 조절에 미치는 영향)

  • Yang, Dae-Seung;Kim, Hyun-A;Hyun, Ha-Na;You, Hyung-Keun;Kim, Youn-Chul;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.32 no.4
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    • pp.811-825
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    • 2002
  • 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. Cervi Parvum Comu(CPC) have been traditionally study as an hale, growth. hematogenous, anti-aging, hack pain in Eastern medicine. The purpose of present study was to investigate the effects of CPC extract on cell cycle progression and its molecular mechanism in human fetal osteoblasts. CPC extracts (10 ${\mu}g/ml$) increased cell proliferation in the human fetal osteoblasts compared to non-supplemented control. There was no significant change in the G1 and S phase, hut a increase in the G2/M phase in 10 ${\mu}g/ml$ and 100 ${\mu}g/ml$ of CPC extracts group as compared to non-supplemented control. The protein expression of cyclin E, cdk 2, cycln D, cdk 4, and cdk 6 was higher than that of control group. The level of p21 was lower than that of control. But that of pRb and pl6 was not distinguished from control. These results indicate that the increase of cell proliferation by CPC extracts may be due t o the increased expression of cyclin E, cdk 2, cyclin D, cdk 4 and cdk 6, and the decreased expression of p21 in human fetal osteoblasts.

Tumor suppressor $p16^{INK4a}$ in Cancer

  • Lee, Mee-Hyun;Choi, Bu-Young;Surh, Young-Joon
    • Environmental Mutagens and Carcinogens
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    • v.25 no.3
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    • pp.87-96
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    • 2005
  • [ $p16^{INK4a}$ ] is a tumor suppressor that belongs to the INK4 family of the cyclin D-dependent kinases (cdk) inhibitors. It plays regulatory roles in cell proliferation and in tumorigenesis by interacting with Rb signaling. Abnormally elevated $p16^{INK4a}$ protein expression causes cell cycle arrest (G1/S transition) and loss of cyclin-cdk activity. In many cancers, $p16^{INK4a}$ is altered by mutation, deletion, and promoter methylation. This review summarizes the function of p16 as an important regulator of cancer pathobiology and a promising target fer developing cancer therapeutic and chemopreventive agents.

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A Simple and Efficient Docking Method to the Cyclin-Dependent Kinase 2

  • Park, Kwang-Su;Kim, Jin-Young;Chong, You-Hoon;Choo, Hyun-Ah
    • Bulletin of the Korean Chemical Society
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    • v.28 no.2
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    • pp.211-219
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    • 2007
  • The subtle but significant differences and thereby the lack of consensus in active site structures among the crystal structures of cyclin-dependent kinase 2 (CDK2) has hampered structure-based drug design. In this study, we devised a simple but effective ‘mutation, pharmacophore-guided docking, followed by mutation' strategy to generate an “average” CDK2 structure, which was used for ligand docking study to successfully reproduce 30 out of 32 X-ray ligand positions within 2.0 A of heavy atom RMSD. This novel docking method was applied for structure-based 3D QSAR with CoMSIA study of a series of structurally related ligands, which showed a good discrimination between CDK2 binders and nonbinders.

Studies on the effect of Betula platyphylla extract on human dermal papilla cell proliferation and its mechanism of action (자작나무 추출물에서 보이는 모유두(HDP) 세포 성장 촉진 효과와 작용 메커니즘 연구)

  • Seunghyun Ahn;Jung Yeon Lee;Eunbi Hong;Jiyun Kim;Won Seok Jeong;Kown Ki Moon;CheongTaek Kim;Jiha Sung;Seyeon Park
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.269-275
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    • 2022
  • Betula platyphylla extract includes various materials which showed biological activity such as terpenoids. For this reason, Betula platyphylla extract has been used to alleviate inflammation. In this study, extract of Betula platyphylla was obtained and purified using several solvents and evaluated whether they showed effect on prevention of hair loss. Cell cytotoxicity assay was performed to investigate the effect of extracts on cell proliferation. Western blotting was performed to observe the changes in expression of several related growth factors such as β-catenin, VEGF, IGF1, and cyclin D. Also, 5-α-reductase activity was measured. The ethyl acetate extract was divided into four partial extracts and named as H3-1, H3-2, H3-3, and H3-4. The H3-2 extract showed proliferation activity of human derma papilla cell and increased the protein expression of several related growth factors such as β-catenin, VEGF, IGF1, and cyclin D, comparable to the effect of Ethyl 3,4,5-Trimethoxy Benzoate (ETB)and Lupeol (LPO). Moreover, we found that the fraction H3 was shown to decrease 5-α-reductase activity while ETB and LPO had no significant effect on 5-α-reductase activity.

Orostachys japonicus DW and EtOH Extracts Induce Apoptosis in Cholangiocarcinoma Cell Line SNU-1079

  • Choi, Eun Sol;Lee, Jang Hoon
    • The Journal of Korean Medicine
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    • v.36 no.4
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    • pp.19-34
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    • 2015
  • Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.

Enhanced Anti-tumor Efficacy of Aspirin Combined with Triptolide in Cervical Cancer Cells

  • Chen, Rong-Hui;Tian, Yong-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3041-3044
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    • 2013
  • Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

Up-Regulation of $p27^{Kip1}$ Protects hES Cells from Differentiation-Associated and Caspase 3-Dependent Apoptosis

  • Park, So-Hyun;Kim, Min Kyoung;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1790-1794
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    • 2012
  • Recently, it has been suggested that $p27^{Kip1}$, the cell cycle regulatory protein, plays a pivotal role in the progression of normal differentiation in murine embryonic stem (mES) cells. In the current study, we investigated the role of $p27^{Kip1}$ in the regulation of differentiation and apoptotic induction using Western blotting, quantitative real-time RT-PCR, and small interfering RNA (siRNA) assays and confocal laser scanning microscopic analysis of H9 human ES (hES) cells and H9-derived embryoid bodies (EBs) grown for 10 ($EB_{10}$) and 20 days ($EB_{20}$). Our results demonstrate that the proteins $p27^{Kip1}$ and cyclin D3 are strongly associated with cellular differentiation, and, for the first time, show that up-regulation of $p27^{Kip1}$ protects hES cells from inducing differentiation-associated and caspase 3-dependent apoptosis.

Suppression of MCF-7 Human Breast Cancer Cell Proliferation by Globefish Takifugu obscurus Homogenate (복어(Takifugu obscurus) 균질액에 의한 MCF-7 인간 유방암세포 성장 억제 효과)

  • Kim, Junghoon;Kim, Jungho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.53 no.6
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    • pp.878-885
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    • 2020
  • Previously, we reported that globefish Takifugu obscurus homogenate suppresses the growth of human colorectal cancer cells. To extend the applications of globefish homogenate, we investigated its cytotoxic effects on human breast cancer cells. To assess the effects of globefish homogenate on growth of MCF (Michigan Cancer Foundation)-7 human breast cancer cells, cell proliferation and colony formation assays were performed using the cell counting and Crystal Violet staining methods. The 50% inhibitory concentration (IC50) of globefish homogenate on MCF-7 cell proliferation was calculated from the sigmoidal dose-response curve. The colony formation assay demonstrated that MCF-7 cells treated with globefish homogenate formed up to 80% fewer colonies than control MCF-7 cells. Treatment with globefish homogenate markedly suppressed the growth of MCF-7 cells in a dose-dependent manner. The sensitivity of the cells to globefish homogenate was determined by calculating the IC50; in this case, the IC50 was 210 ㎍/mL. Furthermore, significant downregulation of Cyclin D1 expression, along with phospho-Akt and total Akt levels, was observed in MCF-7 cells treated with globefish homogenate. This study demonstrates that treatment with globefish homogenate inhibits the proliferation of MCF-7 human breast cancer cells by downregulating the expression of phosphor-Akt, total Akt, and Cyclin D1 proteins.

IMMUNIES, a unique polyherbal extract, exhibits antiproliferative activity and improves tumor-bearing canine patients: a pilot study

  • Won Seok Oh;Ilju Kim;Jiyoung Moon;Seung Joon Baek
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.379-387
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    • 2023
  • Dog owners seek treatment when their pets develop cancer. IMMUNIES is traditional herbal medicine-based figment made of 10 natural herbs, designed to maintain host immune function. The major component of IMMUNIES is Dendropanax morbiferus. This clinical pilot study monitored the toxicity and efficacy of IMMUNIES. Four senile dogs with spontaneously occurring mammary and liver cancers were enrolled in this study and treated orally daily for 3 months, and their blood/urine biochemical profiles were examined each month. IMMUNIES was well tolerated during the treatment period. Blood urea nitrogen, creatinine, alanine aminotransferase, alkaline phosphatase, and C-reactive protein levels decreased in all four dogs, whereas red blood cells and hematocrit were within the normal range. IMMUNIES also changed the expression of several molecular targets in the anticancer pathway, such as pro-NAG-1, p53, and cyclin D1. Although the tumors did not completely respond to IMMUNIES, the biochemical profiles and clinical examination showed a stabilized cancer status for 3 months. Thus, IMMUNIES was found to be safe and well-tolerated in the dosage range tested and exhibited cancer antiproliferative activity in canine cancer. Future studies should address other potential benefits of IMMUNIES, including correlative assessments of immune function, quality of life, and owner satisfaction.