• Title/Summary/Keyword: Agent Migration

Search Result 216, Processing Time 0.025 seconds

Luteolin Arrests Cell Cycling, Induces Apoptosis and Inhibits the JAK/STAT3 Pathway in Human Cholangiocarcinoma Cells

  • Aneknan, Ploypailin;Kukongviriyapan, Veerapol;Prawan, Auemduan;Kongpetch, Sarinya;Sripa, Banchob;Senggunprai, Laddawan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.12
    • /
    • pp.5071-5076
    • /
    • 2014
  • Cholangiocarcinoma (CCA) is one of the aggressive cancers with a very poor prognosis. Several efforts have been made to identify and develop new agents for prevention and treatment of this deadly disease. In the present study, we examined the anticancer effect of luteolin on human CCA, KKU-M156 cells. Sulforhodamine B assays showed that luteolin had potent cytotoxicity on CCA cells with IC50 values of $10.5{\pm}5.0$ and $8.7{\pm}3.5{\mu}M$ at 24 and 48 h, respectively. Treatment with luteolin also caused a concentration-dependent decline in colony forming ability. Consistent with growth inhibitory effects, luteolin arrested cell cycle progression at the G2/M phase in a dose-dependent manner as assessed by flow cytometry analysis. Protein expression of cyclin A and Cdc25A was down-regulated after luteolin treatment, supporting the arrest of cells at the G2/M boundary. Besides evident G2/M arrest, luteolin induced apoptosis of KKU-M156 cells, demonstrated by a distinct sub-G1 apoptotic peak and fluorescent dye staining. A decrease in the level of anti-apoptotic Bcl-2 protein was implicated in luteolin-induced apoptosis. We further investigated the effect of luteolin on JAK/STAT3, which is an important pathway involved in the development of CCA. The results showed that interleukin-6 (IL-6)-induced JAK/STAT3 activation in KKU-M156 cells was suppressed by treatment with luteolin. Treatment with a specific JAK inhibitor, AG490, and luteolin diminished IL-6-stimulated CCA cell migration as assessed by wound healing assay. These data revealed anticancer activity of luteolin against CCA so the agent might have potential for CCA prevention and therapy.

Anti-metastatic Potential of Ethanol Extract of Saussurea involucrata against Hepatic Cancer in vitro

  • Byambaragchaa, Munkhzaya;de la Cruz, Joseph;Yang, Seung Hak;Hwang, Seong-Gu
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.9
    • /
    • pp.5397-5402
    • /
    • 2013
  • The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

Effect of Trametes cubensis Extract on Vascular Function of Bovine Aortic Endothelial Cells (Trametes cubensis 버섯 추출물이 소의 대동맥 내피세포의 혈관 기능에 미치는 효능)

  • Jang, Sujeong;Lee, Dong Hyeung;Kim, Seong Hwan;Park, Heonyong
    • The Korean Journal of Mycology
    • /
    • v.48 no.1
    • /
    • pp.1-13
    • /
    • 2020
  • Mushrooms have been extensively used as traditional medicines to treat cancer and inflammatory diseases. In this study, we examined whether Trametes cubensis extract (TCE) exerted beneficial effects on cardiovascular function. First, we demonstrated that TCE was non-cytotoxic and enhanced cell proliferation of bovine aortic endothelial cells (BAEC). Moreover, TCE induced cell migration and blocked lipopolysaccharide-induced adhesion of monocytes to BAEC. We performed a variety of cell signaling studies, showing that TCE activates p38 MAPK and generates reactive oxygen species (ROS). Our results showed that TCE-induced vascular functions were mediated by p38 MAPK, but not by ROS. These results provide insights into bio-medical applications of TCE as a preventive or therapeutic agent for treating cardiovascular diseases including atherosclerosis.

Genotoxicity of Taxol and 10-Deacetyl Baccatin III Using Single Cell Gel Electrophoresis (Comet Assay) in Chinese Hamster Lung Fibroblast

  • Kim, Hyun-Joo;Kim, Kyung-Ran;Youn, Ji-Youn;Kim, Min-Hee;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
    • /
    • 1996.12a
    • /
    • pp.61-61
    • /
    • 1996
  • Taxol is used as cancer therapeutic agent. It has been known as weak posotive of chromosome aberration assay in vitro in our previous results (Ryu et al., 1996) and potent clastogens in the mouse bone marrow micronucleus (Tinwell and Ashby, 1994). We performed microgel electrophoresis to determine the effect of taxol and it's precursor 10-deacetyl baccatin III(DAB) on DNA. Microgel electrophoresis is useful, rapid, simple, visual, and sensitive technique for measuring DNA breakage and repair mechanisms in mammalian 근ells. The range of concentration used for taxol were 854, 427, 213.5, 106.8, 53.4 Ug/ml, for DAB 910 ,455, 227.5 U9/ml, Cell viability always exceed 85%. We analyzed the results by using the special software of image analyzer for this comet assay (Komet 3.0). By using this image analyzer software , we can get the result as the tail moment ((mean of tail length - mean of head lengh) x tail%DNA/100). A slight increase in DNA migration was observed for taxol at the concentration of 854 Ug/m4 in the absence of S9 mixture. No increased DNA migration was observed after treatment with DAB.

  • PDF

Study for Possibility of N,N,N-Trimethylphytosphingosine (TMP) for Management of Chronic Skin Diseases (N,N,N-Trimethylphytosphingosine (TMP)의 염증성 피부질환 치료제 가능성에 관한 연구)

  • Seo, Won-Sang;Oh, Han-Na;Park, Woo-Jung;Um, Sang-Young;Kang, Sang-Mo
    • KSBB Journal
    • /
    • v.29 no.1
    • /
    • pp.36-41
    • /
    • 2014
  • Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

Simultaneous Inhibition of CXCR4 and VLA-4 Exhibits Combinatorial Effect in Overcoming Stroma-Mediated Chemotherapy Resistance in Mantle Cell Lymphoma Cells

  • Kim, Yu-Ri;Eom, Ki-Seong
    • IMMUNE NETWORK
    • /
    • v.14 no.6
    • /
    • pp.296-306
    • /
    • 2014
  • There is growing evidence that crosstalk between mantle cell lymphoma (MCL) cells and stromal microenvironments, such as bone marrow and secondary lymphoid tissues, promotes tumor progression by enhancing survival and growth as well as drug resistance of MCL cells. Recent advances in the understanding of lymphoma microenvironment have led to the identification of crucial factors involved in the crosstalk and subsequent generation of their targeted agents. In the present study, we evaluated the combinatory effect of blocking antibodies (Ab) targeting CXCR4 and VLA-4, both of which were known to play significant roles in the induction of environment-mediated drug resistance (EMDR) in MCL cell line, Jeko-1. Simultaneous treatment with anti-CXCR4 and anti-VLA-4 Ab not only reduced the migration of Jeko-1 cells into the protective stromal cells, but also enhanced sensitivity of Jeko-1 to a chemotherapeutic agent to a greater degree than with either Ab alone. These combinatorial effects were associated with decreased phosphorylation of ERK1/2, AKT and NF-${\kappa}B$. Importantly, drug resistance could not be overcome once the adhesion of Jeko-1 to the stromal occurred despite the combined use of Abs, suggesting that the efforts to mitigate migration of MCLs should be attempted as much as possible. Our results provide a basis for a future development of therapeutic strategies targeting both CXCR4 and VLA-4, such as Ab combinations or bispecific antibodies, to improve treatment outcomes of MCL with grave prognosis.

Radiologic Abnormalities in Prolonged SARS-CoV-2 Infection: A Systematic Review

  • Kyongmin Sarah Beck;Jeong-Hwa Yoon;Soon Ho Yoon
    • Korean Journal of Radiology
    • /
    • v.25 no.5
    • /
    • pp.473-480
    • /
    • 2024
  • We systematically reviewed radiological abnormalities in patients with prolonged SARS-CoV-2 infection, defined as persistently positive polymerase chain reaction (PCR) results for SARS-CoV-2 for > 21 days, with either persistent or relapsed symptoms. We extracted data from 24 patients (median age, 54.5 [interquartile range, 44-64 years]) reported in the literature and analyzed their representative CT images based on the timing of the CT scan relative to the initial PCR positivity. Our analysis focused on the patterns and distribution of CT findings, severity scores of lung involvement on a scale of 0-4, and the presence of migration. All patients were immunocompromised, including 62.5% (15/24) with underlying lymphoma and 83.3% (20/24) who had received anti-CD20 therapy within one year. Median duration of infection was 90 days. Most patients exhibited typical CT appearance of coronavirus disease 19 (COVID-19), including ground-glass opacities with or without consolidation, throughout the follow-up period. Notably, CT severity scores were significantly lower during ≤ 21 days than during > 21 days (P < 0.001). Migration was observed on CT in 22.7% (5/22) of patients at ≤ 21 days and in 68.2% (15/22) to 87.5% (14/16) of patients at > 21 days, with rare instances of parenchymal bands in previously affected areas. Prolonged SARS-CoV-2 infection usually presents as migrating typical COVID-19 pneumonia in immunocompromised patients, especially those with impaired B-cell immunity.

Evaluation Method of Self-healing Performance of Cement Composites (시멘트 복합체의 자기치유 성능평가 방법)

  • Lee, Kwang-Myong;Kim, Hyung-Suk;Min, Kyung-Sung;Choi, Sung
    • Journal of the Korean Recycled Construction Resources Institute
    • /
    • v.8 no.1
    • /
    • pp.134-142
    • /
    • 2020
  • In this study, in order to evaluate the self-healing performance of cement composites the self-healing test method and the analysis method were suggested by applying constant water head permeability test, chloride migration test and repeated bending test. The method of making a cracked specimen and controlling crack width are also proposed. Constant head water permeability test can evaluate the healing performance by using the decreasing rate of water flow passing through the crack zone of a specimen. Furthermore, the equivalent crack width can be used to intuitively investigate the healing effect with healing period. The chloride migration test can evaluate the healing rate by the decreasing rate of the diffusion coefficient obtained by ASTM C 1202. Mechanical healing performance can be evaluated using ISR and IDR estimated from load vs. CMOD relationship graph obtained through the repeated bending test. Finally, the applicability of proposed self-healing evaluation methods was examined by testing mortar specimens with or without self-healing agents.

Silymarin Attenuates Invasion and Migration through the Regulation of Epithelial-mesenchymal Transition in Huh7 Cells (간암세포주에서 상피간엽전환억제를 통한 Silymarin의 침윤 및 전이 억제 효과)

  • Kim, Do-Hoon;Park, So-Jeong;Lee, Seung-Yeon;Yoon, Hyun-Seo;Park, Chung Mu
    • Korean Journal of Clinical Laboratory Science
    • /
    • v.50 no.3
    • /
    • pp.337-344
    • /
    • 2018
  • Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

The Effect of Entrained Air Contents on the Properties of Freeze-thaw Deterioration and Chloride Migration in Marine Concrete (연행 공기량이 해양콘크리트의 동결융해 및 염화물 확산특성에 미치는 영향)

  • Park, Sang-Joon
    • Journal of the Korea institute for structural maintenance and inspection
    • /
    • v.12 no.5
    • /
    • pp.161-168
    • /
    • 2008
  • The freeze-thaw deterioration and chloride attack, which are the typical degradation factors for durability of marine concrete, are significantly affected by pore structures in terms of penetration and diffusion. These pore structures of concrete are closely related to the types and amount of AE agent, used to guarantee the resistance of freeze-thaw deterioration, and the elapsed time before concrete pouring. This paper evaluates the durability of concrete based on the results of tests on cylinder specimens and core specimens from mock-up members with different air content of 4~6% and 8~10%, respectively. According to the test results, the air content of hardened concrete is 2.5~5.2% at 7 days and 2.4~5.1% at 28 days. These air contents are about half of the initial values just after the concrete mixing. Judging from the amount of scale after the freeze-thaw test completed, air content of 8~10% is slightly more beneficial against the deterioration of concrete than air content of 4~6%. Meanwhile, the core specimens from mock-up members exhibit somewhat unfavorable freeze-thaw deterioration and chloride migration characteristic compared with the cylinder specimens tested in the laboratory under the same mixing condition, as to show 106% in freeze-thaw test and 160% in chloride diffusion coefficient test, respectively.