• Title, Summary, Keyword: inhibition of proliferation

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Decreased Contact Inhibition in Mouse Adipose Mesenchymal Stem Cells

  • Jeon, Yunmi;Lee, Myung Sook;Cheon, Yong-Pil
    • Development and Reproduction
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    • v.16 no.4
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    • pp.329-338
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    • 2012
  • The proliferation of embryonic cells or adult stem cells in tissue is critically regulated during development and repair. How limited the proliferation of cells, so far, is not much explored. Cell-cell contact proliferation inhibition is known as a crucial mechanism regulating cell proliferation in vitro and in vivo. In this study we examined the characters of mouse subcutaneous adipose derived stem cells (msADSC) whether they lost or get contact inhibition during in vitro culture. The characters of msADSC growth after confluence were analyzed using confocal microscope and the expression profiles of contact inhibition related genes were analyzed according to the morphological changes using real-time PCR method. msADSC showed overlapping growth between them but not after passage 14. The cell shapes were also changed after passage 14. The expression profiles of genes which are involved in contact inhibition were modified in the msADSC after passage 14. The differentiation ability of msADSCs to adipocyte, chondrocyte and osteocyte was not changed by such changes of gene expression profiles. Based on these results, it is revealed that smADSC were characterized by getting of strong cell-cell contact inhibition after passage 14 but the proliferation and developmental ability were not blocked by the change of cell-cell contact proliferation inhibition. These finding will help to understand the growth of adipose tissue, although further studies are needed to evaluate the physiological meaning of the cell-cell contact proliferation inhibition during in vitro culture of msADSC.

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

  • Park, Hyoung-Kwun;Ju, Sung-Min;Kang, Min-Soo;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.26 no.4
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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.

Effects of the Petroleum-ether Extract of Ginseng on the Cell Cycle and Protein Kinase C Activity in Cancer Cells (인삼 Petroleum-ether 추출물이 종양세포의 증식 주기 진행 및 Protein Kinase C의 활성에 미치는 영향)

  • 박민경;황우익
    • Journal of Ginseng Research
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    • v.20 no.3
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    • pp.219-225
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    • 1996
  • This study was performed to investigate the inhibition mechanism of cancer cell proof iferation caused by the petroleum-ether extract of ginseng against human rectum (HRT-18), colon (HT-29), llepatoma (Hep G2) and prostate (LNCaP) cancer cells and monkey kidney cells (Vero 76). Cells were treated with the petroleum-ether extract of ginseng (50 to 200 $\mu\textrm{g}$/ml) in G1 or S phase of the cell cycle, and proliferation and protein kinase C activity were measured. The petroleum-eth or extract of ginseng inhibited proliferation of HRT-18, HT-29, Hep G2 and LNCaP when treated in Gl phase, but not in S phase. This result shows that the ginseng extract arrests the cell cycle in G1 phase, resulting in the inhibition of cell proliferation. At the same concentrations, treatment of the ginseng extract in G1 phase decreased protein kinase C activity, while the treatment in S phase had no effect. This reault suggests that protein kinase C might be involved in the inhibition of the cell cycle and proliferation of cancer cells caused by the petroleum-ether extract of ginseng.

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Losartan Inhibits Vascular Smooth Muscle Cell Proliferation through Activation of AMP-Activated Protein Kinase

  • Kim, Jung-Eun;Choi, Hyoung-Chul
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.5
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    • pp.299-304
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    • 2010
  • Losartan is a selective angiotensin II (Ang II) type 1 ($AT_1$) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the $G_0/G_1$ cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.

Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1

  • Kim, Jung-Eun;Sung, Jin-Young;Woo, Chang-Hoon;Kang, Young-Jin;Lee, Kwang-Youn;Kim, Hee-Sun;Kwun, Woo-Hyung;Choi, Hyoung-Chul
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.4
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    • pp.203-210
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    • 2011
  • Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. We investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose- and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.

Involvement of NAD(P)H Oxidase in a Potential Link between Diabetes and Vascular Smooth Muscle Cell Proliferation

  • Jeong, Hye-Young;Yun, Mi-Ran;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.2
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    • pp.103-109
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    • 2003
  • The cellular mechanisms that contribute to the acceleration of atherosclerosis in diabetes are poorly understood. Therefore, the potential mechanisms involved in the diabetes-dependent increase in vascular smooth muscle cell (VSMC) proliferation was investigated. Using primary culture of VSMC from streptozotocin-induced diabetic rat aorta, cell proliferation assay showed two-fold increase in cell number accompanied with enhanced superoxide generation compared to normal VSMC, 2 days after plating. Both the increased superoxide production and cell proliferation in diabetic VSMC were significantly attenuated by not only tiron (1 mM), a superoxide scavenger, but also by diphenyleneiodonium (DPI; $10{\mu}M$), an NAD(P)H oxidase inhibitor. NAD(P)H oxidase activity in diabetic VSMC was significantly higher than that in control cell, accompanied with increased mRNA expression of p22phox, a membrane subunit of oxidase. Furthermore, inhibition of p22phox expression by transfection of antisense p22phox oligonucleotides into diabetic VSMC resulted in a decrease in superoxide production, which was accompanied by a significant inhibition of cell proliferation. Based on these results, it is suggested that diabetes-associated increase in NAD(P)H oxidase activity via enhanced expression of p22phox contributes to augmented VSMC proliferation in diabetic rats.

Antiestrogen, Trans-Tamoxifen Modulation of Human Breast Cancer Cell Growth

  • Lee, Hyung-Ok;Sheen, Yhun-Yhong
    • Archives of Pharmacal Research
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    • v.20 no.6
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    • pp.572-578
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    • 1997
  • To gain further insight into how antiestrogens modulate cell function, the effects of antiestrogen on cell proliferation were studied in human breast cancer cells. We examined the effects of trans-tamoxifen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Trans-tamoxifen $(1{\mu}M)$ markedly inhibited the estrogen stimulated proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $(1.15{\pm}0.03 pmole/mg protein)$ over that of control. In T47D cells that contained low levels of estrogen receptor $(0.23{\pm}0.05 pmole/mg protein)$, trans-tamoxifen $(1{\mu}M)$ showed minimal inhibition of estrogen stimulated cell proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by trans-tamoxifen treatment. These results showed their sensitivity to growth inhibition by antiestrogen conrrelated well with their estrogen receptor content. Also we examined the effect of antiestrogen on cellular progestrone receptor level as well as plasminogen activator activity in MCF-7 cells. Trans-tamoxifen $(1{\mu}M)$ showed maximal inhibition of estrogen stimulated progestrone receptor level as well as plasminogen activator activity in MCF-7 cells that were stimulated by estrogen. It is not clear whether these inhibitions of progestrone receptor and plasminogen activator activity by estrogen are related to the antiestrogen inhibition of cell proliferation of MCF-7 cells. From the results of this study, it is clearly demonstrated that trans-tamoxifen is an antiestrogen in MCF-7 human breast cancer cells. Our data suggest that the biological effectiveness of trans-tamoxifen appear to result from its affinity of interaction with the estrogen receptor.

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Inhibitory Effects of Rehmannia glutinosa Liboschitz on Endothelial Cell Proliferation

  • Lee, Sung-Jin;Lee, Hak-Kyo
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.5
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    • pp.311-314
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    • 2007
  • Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

Lisophosphatidic Acid Inhibits Melanocyte Proliferation via Cell Cycle Arrest

  • Kim, Dong-Seok;Park, Seo-Hyoung;Kim, Sung-Eun;Kwon, Sun-Bang;Park, Eun-Sang;Youn, Sang-Woong;Park, Kyoung-Chan
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1055-1060
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    • 2003
  • Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types. However, we found that LPA inhibits melanocyte proliferation. Thus, we further investigated the possible signaling pathways involved in melanocyte growth inhibition. We first examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were observed in concert with the inhibition of melanocyte proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA. However, the specific inhibition of the ERK or JNK pathways by PD98059 or D-JNKI1, respectively, did not restore the antiproliferative effect. We next examined changes in the expression of cell cycle related proteins. LPA decreased cyclin $D_1 and cyclin D_2$ levels but increased $p21^{WAF1/CIP1}$ (p21) and $p27^{KIP1}$ (p27) levels, which are known inhibitors of cyclin-dependent kinase. Flow cytometric analysis showed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the $G_0/G_1$ phase of the cell cycle. Our results suggest that LPA induces cell cycle arrest by regulating the expressions of cell cycle related proteins.

Effect of Retinoids on Human Breast Cancer Cells (인체 유방암 세포에서 retinoids의 영향에 대한 연구)

  • 윤현정;신윤용;공구
    • Environmental Mutagens and Carcinogens
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    • v.24 no.2
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    • pp.51-66
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    • 2004
  • Retinoids, better known as vitamin A, have been reported to inhibit the growth of several breast cancer cell lines in culture and to reduce breast tumor growth in animal models. Furthermore, retinoids can augment the action of other breast cancer cell growth inhibitors both in vitro and in vivo. Clinically, interest has increased in the potential use of retinoids for the prevention and treatment of human breast cancer. We have examine the effect of all-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) on human breast cancer cell(MCF-10A, T47-D, MCF-7) proliferation using MTT assay and cell cycle analysis(FACS). Overexpression of cyclin D1 protein is observed in the majority of breast cancers, suggesting that dysregulated expression of cyclin D1 might be a critical event in breast cancer carcinogenesis. We investigated whether tRA and 9-cis RA might affect expression of cyclin D1 on human breast cancer cells(MCF-10A, T47-D, MCF-7) using RT-PCR and west-ern bolt. In MCF-10A cells, either tRA or 9-cis RA treatment did not affect the cell proliferation. In T47-D cells and MCF-7 cells, either tRA or 9-cis RA treatment showed the inhibition of the cell proliferation over control cells and also inhibit the estrogen stimulated cell proliferation when it was given together with estrogen. The effect of retinoids was dose- and time- dependent. T47-D cells treated with 1.0 $\muM$ tRA undergo G0/G1-phase arrest by Day 5. MCF-7 cells treated with 1.0 $\muM$ tRA undergo S-phase arrest by Day 5. All-trans retinoic acid(tRA) and 9-cis retinoic acid(9-cis RA) inhibited the cyelin D1 mRNA and protein expression levels of human MCF-7 and T47-D breast carcinoma cells in vitro. The data indicate that retinoids can reduce cyclin D1 expression levels in a variety of breast cell lines in vitro and result in inhibition of cell proliferation. tRA-mediated growth inhibition and cyclin D1 expression inhibition is more potent than 9-cis RA mediated that. tRA-mediated inhibition effect is more potent on T47-D cells than on MCF-7 cells. Our data suggest that retinoids activity is different according to property of cell lines. Future chemoprevention of breast cancer studies using retinoids will be necessary to determine the mechanism of the retinoids-mediated growth inhibition.

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