• Title/Summary/Keyword: cell-cycle inhibition

검색결과 435건 처리시간 0.029초

Downregulation of Cdk1 and CyclinB1 Expression Contributes to Oridonin-induced Cell Cycle Arrest at G2/M Phase and Growth Inhibition in SGC-7901 Gastric Cancer Cells

  • Gao, Shi-Yong;Li, Jun;Qu, Xiao-Ying;Zhu, Nan;Ji, Yu-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권15호
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    • pp.6437-6441
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    • 2014
  • Background: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has antitumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. Materials and Methods: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. Results: Oridonin could inhibit SGC-7901 cell proliferation, the $IC_{50}$ being $15.6{\mu}M$, and blocked SGC-7901 cell cycling in the $G_2/M$ phase. The agent also decreased the protein expression of cyclinB1 and CDK1. Conclusions: Oridonin may inhibit SGC-7901 growth and block the cells in the $G_2/M$ phase by decreasing Cdk1 and cyclinB1 proteins.

길경탕(桔梗湯)이 인체(人體) 폐세포(肺細胞)에 미치는 영향(影響)에 관(關)한 분자생물학적(分子生物學的) 연구(硏究) (Molecular Biological Study of The Effects of Gilgyung-Tang(GGT) on Cellular Proliferation and Viability of Normal Human Lung Fibriblast Cell)

  • 이형구
    • 대한한의학회지
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    • 제20권2호
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    • pp.88-97
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    • 1999
  • To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.

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인진청간탕가미방(茵陳淸肝湯加味方)이 간세포활성(肝細胞活性), 세포주기(細胞週期) 및 APOPTOSIS에 미치는 영향(影響) (The Effects of Injinchunggantang-derivative on Cell Viability, Cell Cycle Progression and Apoptosis of Hepatocytes)

  • 홍상훈;이장훈;우홍정
    • 대한한의학회지
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    • 제19권2호
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    • pp.337-372
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    • 1998
  • To evaluate the effects of Injinchunggantang-derivative on cell viability, cell cycle progression, and apoptosis, MTT assay, cell cycle analysis, Cpp32 protease assay, DNA fragnemtation assay, quantitative RT-PCR, and Western blotting were performed. The results were as followes. In MTT assay, etoposide+Injinchunggantang-derivative-treated cells as well as Injinchunggantang-derivative-treated cells showed higher viability than etoposide-treated cells with no time-concentration-dependence, which implied that Injinchunggantang-derivative has hepato-protective effect Cell cycle analysis showed that Injinchunggantang-derivative has no significant effect on the cell cycle. Cpp32 protease assav and DNA fragmentation assay Injinchunggantang-derivative carry inhibitory effects on apoptosis induction. It was suggested that Injinchunggantang-delivative might regulate the cell cycle, in particular $G_1$ checkpoint by blocking p53 and Watl pathway. Injinchunggantang-derivative inhibited the mRNA expressions of Cpp32, Fas, and Bcl-2, which could result in inhibition of apoptosis. These results imply that Injinchunggantang-derivative increases hepatocyte viability, and protects hepatocyte from damage by regulating the expression of genes associated with cell cycle and apoptosis, which explains the mechanism of the clinical effect of Injinchunggantang-derivative on liver diseases.

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계혈등 추출물이 Jurkat T 임파구의 세포고사 및 세포주기 억제에 미치는 효과 (Spatholobus suberectus Water Extract induces Apoptotic Cell Death via Inhibition of Cell Cycle in Jurkat Human Leukemia Cell Line)

  • 조남수;정우철;나헌식;송영준;이계승;이인;전병훈;문병순
    • 동의생리병리학회지
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    • 제18권1호
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    • pp.101-109
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    • 2004
  • Spatholobus suberectus belonging the family Leguminosae has been used for promoting blood circulation, removing blood stasis, tonifying the blood, relaxing tendons, stopping internal bleeding and eliminating dampness in oriental traditional medicine. This study investigates whether the water extracts of S. suberectus induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by S. suberectus, as measured by cell morphology. The capability of S. suberectus to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly (ADP­ribose)polymerase protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of S. suberectus on cell cycle progression. G1 checkpoin related gene products tested (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2Fl) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by S. suberectus may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

두경부암 세포주에서 상피성장인자수용체 타이로신 카이네이즈 억제제인 gefitinib의 성장억제에 관한 연구 (Growth inhibition in head and neck cancer cell lines by gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor)

  • 송승일;김명진
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제35권5호
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    • pp.287-293
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    • 2009
  • Cell survival is the result of a balance between programmed cell death and cellular proliferation. Cell membrane receptors and their associated signal transducing proteins control these processes. Of the numerous receptors and signaling proteins, epidermal growth factor receptor (EGFR) is one of the most important receptors involved in signaling pathways implicated in the proliferation and survival of cancer cells. EGFR is often highly expressed in human tumors including oral squamous cell carcinomas, and there is increasing evidence that high expression of EGFR is correlated with poor clinical outcome of common human cancers. Therefore, we examined the antiproliferative activity of gefitinib, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), in head and neck cancer cell lines. SCC-9, KB cells were cultured and growth inhibition activity of gefitinib was measured with MTT assay. To study influence of gefitinib in cell cycle, we performed cell cycle analysis with flow cytometry. Western blot was done to elucidate the expression of EGFR in cell lines and phosphorylation of EGFR and downstream kinase protein, Erk and Akt. Significant growth inhibition was observed in SCC-9 cells in contrast with KB cells. Also, flow cytometric analysis showed G1 phase arrest only in SCC-9 cells. In Western blot analysis for investigation of EGFR expression and downstream molecule phosphorylation, gefitinib suppressed phosphorylation of EGFR and downstream protein kinase Erk, Akt in SCC-9. However, in EGFR positive KB cells, weak expression of active form of Erk and Akt and no inhibitory activity of phosphorylation in Erk and Akt was observed. The antiproliferative activity of gefitinib was not correlated with EGFR expression and some possibility of phosphorylation of Erk and Akt as a predictive factor of gefitinib response was emerged. Further investigations on more reliable predictive factor indicating gefitinib response are awaited to be useful gefitinib treatment in head and neck cancer patients.

HK-2 세포에서 indoxyl sulfate로 유도된 세포증식억제에 대한 밀몽화의 효과 (Effect of Buddleja officinalis on the Indoxyl Sulfate-induced Inhibition of Cell Proliferation in HK-2 Cells)

  • 박형권;주성민;강민수;전병훈
    • 동의생리병리학회지
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    • 제26권4호
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    • pp.527-531
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    • 2012
  • The flowers and leaves buds of Buddleja officinalis are used to treat eye troubles, hernia, gonorrhea and liver troubles in Asia. The present study investigated the effect of aqueous extract of Buddleja officinalis (ABO) on indoxyl sulfate (IS)-induced inhibition of cell proliferation in HK-2 cells. The HK-2 cells were incubated with 5 mM IS 5 mM in the absence or presence of ABO (2, 5, 10, 20 ${\mu}g/ml$) for 24 hr. The effect of ABO on IS-treated HK-2 cells was investigated by using MTT assay, flow cytometric analysis and Western blot. IS-induced proliferation inhibition was recovered dose-dependently by treatment with ABO. ABO reduced S and G2/M phase cell cycle arrest induced by IS. Recovery effect of ABO on inhibition of cell proliferation by IS is related to the decrease of p21 expression. Taken together, these results suggest that recovery effect of ABO on proliferation of IS-treated HK-2 cells be associated with cell cycle progression through down-regulation of p21 levels.

The Inhibition Effect of Triptolide on Human Endometrial Carcinoma Cell Line HEC-1B: a in vitro and in vivo Studies

  • Ni, Jing;Wu, Qiang;Sun, Zhi-Hua;Zhong, Jian;Cai, Yu;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권11호
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    • pp.4571-4576
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    • 2015
  • Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

인체 전립선 암세포에서 참나무 목초액에 의한 세포주기 S기 arrest 유발에 관한 연구 (Induction of S phase Arrest of the Cell Cycle by Oak Smoke Flavoring (Holyessing) in Human Prostate Carcinoma Cells)

  • 박철;이원호;최병태;김경철;이용태;최영현
    • 동의생리병리학회지
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    • 제17권5호
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    • pp.1309-1314
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    • 2003
  • We examined the effects of Oak Smoke Flavoring (OSF, Holyessing) on the cell proliferation of DU145 and PC3 human prostate carcinoma cell line. OSF treatment resulted in a concentration-dependent inhibition of the cell viability in both DU145 and PC3 cell lines. The anti-proliferative effects by OSF treatment in DU145 and PC3 cells were associated with morphological changes such as membrane shrinking and cell rounding up. DNA flow cytometric histograms showed that population of S phase of the cell cycle was increased by OSF treatment in a dose-dependent manner. Western blot analysis revealed that cyclin B1 and cdc2 proteins were reduced by OSF treatment in DU145 cells, whereas cyclin A was markedly inhibited in PC3 cells. Furthermore, we observed an increase of Cdk inhibitor p16 and p27 protein, and an inhibition of phosphorylation of pRB by OSF treatment in a dose-dependent manner. The present results indicated that OSF-induced inhibition of human prostate carcinoma cell proliferation is associated with the blockage of S phase progression.

목향(木香)과 차전초(車前草)가 위암세포(胃癌細胞)의 활성(活性), 증식(增殖), 자기살해능(自己殺害能) 및 세포주기관련 유전자 발현에 미치는 영향 (The Effects of Saussurea Radix and Plantaginis Herba on Cellular Viability, Proliferation, Apoptosis and Expression of Cell Cycle-related Genes in Gastric Cancer Cells)

  • 오희라;고성규
    • 대한한방종양학회지
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    • 제7권1호
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    • pp.1-18
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    • 2001
  • Objective: This experimental study was carried out to evaluate the effects of Saussurea Radix and Plantaginis Herba on cellular viability, proliferation, apoptosis and expression of the cell cycle-related genes in cultured gastric cancer cells. Method :MTT assay for analysis of cellular toxicity and the effect on suppression of cellular viability, $[^{3}H]$ thymidine incorporation assay for evaluation of the effect on suppression of DNA replication, tryphan blue exclusion assay for measurement of induction of apoptosis and Quantitative RT-PCR for analysis of the effects on expression of cell cycle or apoptosis-related genes were performed. Results: Antitumor activity of Saussurea Radix associated with inhibition of cell cycle progression and promotion of apoptosis caused by transcriptional regulation of p53, p21/Wafl and the other related genes was observed.

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Apoptotic effect of $IP_6$ was not enhanced by co-treatment with myo-inositol in prostate carcinoma PC3 cells

  • Kim, Hyun-Jung;Jang, Yu-Mi;Kim, Harriet;Kwon, Young-Hye
    • Nutrition Research and Practice
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    • 제1권3호
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    • pp.195-199
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    • 2007
  • Inositol hexaphosphate ($IP_6$) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Previous studies reported the anticancer effect of $IP_6$ and suggested that co-treatment of $IP_6$ with inositol may enhance anticancer effect of $IP_6$. Although the anticancer effect of $IP_6$ has been intensively studied, the combinational effect of $IP_6$ and inositol and involved mechanisms are not well understood so far. In the present study, we investigated the effect of $IP_6$ and myo-inositol (MI) on cell cycle regulation and apoptosis using PC3 prostate cancer cell lines. When cell, were co-treated with $IP_6$ and MI, the extent of cell growth inhibition was significantly increased than that by $IP_6$ alone. To identify the effect of $IP_6$ and MI on apoptosis, the activity of caspase-3 was measured. The caspase-3 activity was significantly increased when cells were treated with either $IP_6$ alone or both $IP_6$ and MI, with no significant enhancement by co-treatment. To investigate the effect of $IP_6$ and MI of cell cycle arrest, we measured p21 mRNA expression in PC3 cells and observed significant increase in p21 mRNA by $IP_6$. But synergistic regulation by co-treatment with $IP_6$ and MI was not observed. In addition, there was no significant effect by co-treatment compared to $IP_6$ treatment on the regulation of cell cycle progression although $IP_6$ significantly changed cell cycle distribution in the presence of MI or not. Therefore, these findings support that $IP_6$ has anticancer function by induction of apoptosis and regulation of cell cycle. However, synergistic effect by MI on cell cycle regulation and apoptosis was not observed in PC3 prostate cancer cells.