• Title/Summary/Keyword: cell cycle control

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Effects of Cervi Parvum Cornu on the Cell Cycle Regulation in Human Periodontal Ligament Cells (녹용이 치주인대세포의 세포주기조절에 미치는 영향)

  • You Seung Han;Choi Hee In;Kim Hyun A;Kim Yun Sang;Shin Hyung Shik;You Hyung Keun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.157-164
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    • 2003
  • Cervi Parvum Cornu(CPC) is that the young horn of deer family and has been traditionally used as a medicine in Eastern. The purpose of present study was to investigate the effects of CPC on cell cycle progression and its molecular mechanism in human periodontal ligament cells (HPOLC). In cell proliferation assay, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1 ㎍/ml and 10 ㎍/ml of CPC were used, all treatment groups increased the cell growth. Maximal cell proliferation was observed in cells exposed to 100 ng/ml of CPC at 4 day, and 10 ng/ml and 100 ng/ml of CPC at 6 days. S phase was increased and G1 phase was decreased in the group treated with 100 ng/ml of CPC in cell cycle analysis. The protein levels of cyclin D1 were not changed, but the levels of cyclin E, cdk 2, cdk 4 and cdk 6 were increased. The protein levels of p21, pRb were decreased as compared to that of control group, but the levels of p53 was not changed in the cells both treated with CPC Md untreated. These results suggested that CPC increases the cell proliferation and cell cycle progression in HPDLC, which is linked to an increased cellular levels of cyclin E, cdk 2, cdk 4 and cdk 6, and decreased the levels of p53, p21.

Flow cytometry of cell-cycle on Flavin mononucleotide (1,4-butanediamine) Pt(II) Complex and Cisplatin and Their Biochemical Analysis of Nephrotoxicity in ICR Mice (Flavin mononucleotide (1,4-butanediamine) Pt(II) Complex와 Cisplatin의 세포주기에 대한 유세포 분석 및 ICR계 생쥐에서의 신장독성에 대한 생화학적 분석)

  • 권영이;황규자;김안근;김국환;김원규;안동춘
    • YAKHAK HOEJI
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    • v.44 no.2
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    • pp.149-154
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    • 2000
  • Flavin mononucleotide (1,4-butanediamine) Pt(II) complex (7FMN) was synthesized and screened anticancer activity [J. Pharm. Soc. Korea 43(6),762-770 (1999)]. 7FMN have good water solubility and moderate anticancer activiy In this paper cell-cycle specificity and nephrotoxicity were studied. Interaction of DNA with cisplatin and synthesized 7FMN was analyzed by flow cytometry and showed G2 arrest in L1210 cell line. It means that cell-cycle on L1210 was inhibit in S phase by cisplatin and 7FMN. In order to biochemically analyze nephrotoxicity of cisplatin and 7FMN, after injecting each agent intraperitoneally, blood was exsanguinated after 6 hours, 1 day, 3 days and 7 days, respectively. Then, serum was separated from the blood. The serum level of BUN, creatinine and uric acid in cisplatin and 7FMN administated mice (25~35 g, ICR strain, a dose each 8,12 and 16 times of the $IC_{50}$/ value, cisplatin; 7 times) were determined by autochemistry analyzer. In cisplatinadministered mice group, BUN level was elevated than normal control group at 3rd day and repaired at 7th day. In 7FMN administrated group was not elevated. Creatinine and uric acid level were no difference with the normal control group. Therefore synthesized 7FMN is less toxic than cisplatin in nephrotoxiciaty.

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Study of Signaling Pathway on Apoptotic Cell Death Induced by Extract of Ailanthus altissima in Human Jurkat Lymphocytes (저근백피(樗根白皮) 추출물에 의한 급성 림프성 백혈병 Jurkat Lymphocytes의 세포고사 유도 및 신호기전 연구)

  • Lee, Ki Ouk;Kim, Ae Wha;Lim, Kyu Sang;Yun, Young Gab
    • Herbal Formula Science
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    • v.25 no.3
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    • pp.349-362
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    • 2017
  • Objectives : We investigated whether the components of Ailanthus altissima induced apoptotic cell death in Jurkat acute lymphoblastic leukemia (ALL) cells. Methods : Regulation of cell proliferation is a complex process involving the regulated expression and/or modification of discrete gene products, which control transition between different stages of the cell cycle. Results : Upon treatments with Ailanthus altissima, the concentration-dependent inhibitions of cell viability were observed as compared to untreated control group. The capability of Ailanthus altissima to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly(ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Ailanthus altissima also caused apoptosis as measured by cell morphology and DNA fragmentation. Conclusions : These results indicate that the increase of apoptotic cell death by Ailanthus altissima may be due to the inhibition of cell cycle in human Jurkat lymphocytes. Conclusively, these current and further findings will provide novel approaches to understanding and treating major diseases.

Cell Cycle Regulation and Induction of Apoptosis by β-carotene in U937 and HL-60 Leukemia Cells

  • Upadhyaya, K.R.;Radha, K.S.;Madhyastha, H.K.
    • BMB Reports
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    • v.40 no.6
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    • pp.1009-1015
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    • 2007
  • In this communication, we report the efficacy of $\beta$-carotene towards differentiation and apoptosis of leukemia cells. Dose ($20{\mu}M$) and time dependence (12 h) tests of $\beta$-carotene showed a higher magnitude of decrease (significance p < 0.05) in cell numbers and cell viability in HL-60 cells than U937 cells but not normal cell like Peripheral blood mononuclear cell (PBMC). Microscopical observation of $\beta$-carotene treated cells showed a distinct pattern of morphological abnormalities with inclusion of apoptotic bodies in both leukemia cell lines. When cells were treated with $20{\mu}M$ of $\beta$-carotene, total genomic DNA showed a fragmentation pattern and this pattern was clear in HL-60 than U937 cells. Both the cell lines, on treatment with $\beta$-carotene, showed a clear shift in $G_1$ phase of the cell cycle. In addition the study also revealed anti-oxidant properties of $\beta$-carotene since there was reduction in relative fluorescent when treated than the control at lower concentration. Collectively this study shows the dual phenomenon of apoptosis and differentiation of leukemia cells on treatment with $\beta$-carotene.

Extracts of Opuntia humifusa Fruits Inhibit the Growth of AGS Human Gastric Adenocarcinoma Cells

  • Hahm, Sahng-Wook;Park, Jieun;Park, Kun-Young;Son, Yong-Suk;Han, Hyungchul
    • Preventive Nutrition and Food Science
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    • v.21 no.1
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    • pp.31-37
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    • 2016
  • Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF ($100{\mu}g/mL$) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF ($200{\mu}g/mL$) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

Effect of Cyclin D2 on Cell Proliferation in T-47D Breast Cancer Cells (인체 유방암 세포에서 과다발현 시킨 Cyclin D2의 영향에 대한 연구)

  • 김현준;이근수;전상학;공구
    • Environmental Mutagens and Carcinogens
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    • v.24 no.1
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    • pp.1-9
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    • 2004
  • Three D-type cyelins (D1, D2, and D3) are expressed in G1 phase of the cell cyele and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cyele progression and human carcinogenesis. Specially, loss of cyelin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

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Evidence of an Epigenetic Modification in Cell-cycle Arrest Caused by the Use of Ultra-highly-diluted Gonolobus Condurango Extract

  • Bishayee, Kausik;Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.16 no.4
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    • pp.7-13
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    • 2013
  • Objectives: Whether the ultra-highly-diluted remedies used in homeopathy can effectively bring about modulations of gene expressions through acetylation/deacetylation of histones has not been explored. Therefore, in this study, we pointedly checked if the homeopathically-diluted anti-cancer remedy Condurango 30C (ethanolic extract of Gonolobus condurango diluted $10^{-60}$ times) was capable of arresting the cell cycles in cervical cancer cells HeLa by triggering an epigenetic modification through modulation of the activity of the key enzyme histone deacetylase 2 vis-a-vis the succussed alcohol (placebo) control. Methods: We checked the activity of different signal proteins (like $p21^{WAF}$, p53, Akt, STAT3) related to deacetylation, cell growth and differentiation by western blotting and analyzed cell-cycle arrest, if any, by fluorescence activated cell sorting. After viability assays had been performed with Condurango 30C and with a placebo, the activities of histone de-acetylase (HDAC) enzymes 1 and 2 were measured colorimetrically. Results: While Condurango 30C induced cytotoxicity in HeLa cells in vitro and reduced HDAC2 activity quite strikingly, it apparently did not alter the HDAC1 enzyme; the placebo had no or negligible cytotoxicity against HeLa cells and could not alter either the HDAC 1 or 2 activity. Data on $p21^{WAF}$, p53, Akt, and STAT3 activities and a cell-cycle analysis revealed a reduction in DNA synthesis and G1-phase cell-cycle arrest when Condurango 30C was used at a 2% dose. Conclusion: Condurango 30C appeared to trigger key epigenetic events of gene modulation in effectively combating cancer cells, which the placebo was unable to do.

Cell Cycle-Dependent Activity Change of Calcium/Calmodulin-Dependent Protein Kinase II (칼슘/calmodulin-의존적 단백질 인산화 효소 II의 동물세포 주기에 따른 활성도 변화에 관한 연구)

  • Koung, Hoon-Suh
    • The Journal of Natural Sciences
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    • v.9 no.1
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    • pp.1-7
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    • 1997
  • Calcium/calmodulin-dependent protein kinase II (CaMK-II) is responsible for the phosphorylation of proteins involved in various cellular functions. Since the level of intracellular calcium ($Ca_2+$) oscillate during the cell cycle, it is expected that the activity of CaMK-II is also dependent on the cell cycle. The kinase activity in NIH3T3 cells which were arrested at or released from certain phase of the cell cycle was measured and compared to that in the normally growing asynchronous control cells to investigate whether the activity of this kinase is cell cycle-dependent. Cells were arrested at G0, G1, G1/S, G2/M and M phase, respectively by use of various drugs which do not have any effect on the kinase activity of CaMK-II at G0, G1, G1/s and G2/M phase was similar to that of the control cells, whereas lower at M. Calcium-independent activity of CaMK_II by autophosphorylation was higher at M and, thus, higher autonomy at M, which represented the physiologically relevant activity of CaMK-II. A similar pattern of activity change of the kinase was demonstrated during the cell cycle of synchronized cells which were released from G1 arrest. These results indicate that the activity of CaMK-11 is cell cycle-dependent and is activity during the mitosis.

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