• Title/Summary/Keyword: cancer cell proliferation

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Inhibitory Effects and Molecular Mechanism of Adipocyte Differentiation by Rosae laevigata Fructus Ethanol Extracs (금앵자 에탄올 추출물에 의한 3T3-L1 지방세포의 분화억제 효과와 그 메커니즘 규명)

  • Jeong, Hyun Young;Jeong, In Kyo;Nam, So Yeon;Yun, Hee Jung;Kim, Byung Woo;Kwon, Hyun Ju
    • Microbiology and Biotechnology Letters
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    • v.44 no.1
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    • pp.89-97
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    • 2016
  • Obesity is caused by excess accumulation of body fat and contributes to various pathological disorders such as diabetes, hypertension, cardiovascular disease, and cancer. In this study, we investigated the effect of a 30% ethanol extract of Fructus Rosae laevigata (RLE) on adipogenesis in 3T3-L1 adipocytes, measured by triglyceride accumulation and expression of adipogenesis-related transcription factors during differentiation of pre-adipocytes into adipocytes. RLE decreased the intracellular triglyceride contents (assessed by Oil Red-O staining) in a dose-dependent manner. It also downregulated the expression of adipogenic transcription factors and inhibited cell proliferation during the mitotic clonal expansion phase of adipocyte differentiation by inducing G1 phase arrest. We investigated the alterations in the levels of G1 phase arrest-related proteins. The expression of p21 protein significantly increased, while the levels of Cyclin E, Cdk2, and phospho-Rb decreased in a dose-dependent manner in 3T3-L1 cells treated with RLE. These results suggest that RLE inhibits the differentiation of 3T3-L1 adipocytes by suppressing the expression of adipogenic transcription factors and inducing G1 phase arrest in the early stages of adipocyte differentiation.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice

  • Kim, Jo-Heon;Alam, Morshedul;Park, Doek Bae;Cho, Moonjae;Lee, Seung-Hong;Jeon, You-Jin;Yu, Dae-Yeul;Kim, Tae Du;Kim, Ha Young;Cho, Chung Gu;Lee, Dae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.5
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    • pp.455-461
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    • 2013
  • Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

Effect of Dangguibohyultang and its combinations on apoptosis in human colorectal adenocarcinoma HCT116 cells (당귀보혈탕(當歸補血湯)의 배합비율에 따른 대장암 세포주 HCT116의 세포사멸 효과)

  • Kim, Byung-Wan;Yun, Hyun-Joung;Jeon, Hyeon-Suk;Yun, Hyung-Joong;Kim, Chang-Hyun;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.21 no.2
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    • pp.37-46
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    • 2006
  • Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

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The Role of Bmi1 in Pilocarpine-induced Status Epilepticus in Mice (Pilocarpine에 의해 유도된 생쥐 경련중첩증에서 Bmi1의 역할)

  • Pyeon, Hae-In;Bak, Jia;Choi, Yun-Sik
    • Journal of Life Science
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    • v.30 no.6
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    • pp.513-521
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    • 2020
  • B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a polycomb group protein and a core component of polycomb repressive complex 1. Initial research into Bmi1 has focused on its role in tumorigenesis, and it is generally accepted that it is important for the proliferation and survival of cancer cells. However, more recent studies have revealed that Bmi1 is downregulated in brains with neurodegenerative disease and that it regulates the function of mitochondria and reactive oxygen species levels. In this study, we tested the therapeutic potential of Bmi1 in pilocarpine-induced seizures in Bmi1-knockout mice. Bmi1 expression transiently increased in the hippocampal CA1 and CA3 and the dentate gyrus following pilocarpine-induced status epilepticus (SE). In terms of seizure behavior, SE induction was 43.14% and 53.57% for Bmi1+/+ and Bmi1+/- mice, respectively. However, there was no significant difference in mortality or hippocampal damage between the two groups. Two months after SE induction, the frequency of epileptic seizures in the Bmi1+/- mice was 50% lower than in the control group, although the difference was not statistically significant. In addition, mossy fiber outgrowth in the Bmi1+/- mice was significantly higher than in their wild-type littermates. Taken together, these data indicate that reduced Bmi1 activity increases pilocarpine-induced seizure probability and mossy fiber outgrowth.

Anticancer and Immuno-Activities of Edible Crude Saponin from Soybean Cake (대두박으로부터 분리한 식용 조사포닌의 항암 및 면역활성)

  • Park, Kyung-Uk;Wee, Jae-Joon;Kim, Jae-Yong;Jeong, Chang-Ho;Kang, Kap-Suck;Choi, Young-Sook;Seo, Kwon-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.10
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    • pp.1509-1513
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    • 2005
  • To develop a new functional food material, edible crude saponin was isolated from soybean cake using HP-20 resin and its anticancer effect and immune-activity were investigated. The saponin significantly inhibited the growth of cancer cells such as A549, MCF-7 and SW480 at a concentration of 1,000 $\mu$g/mL. Morphological changes was observed in the AS49 cells surface treated with the saponin of 1,000 $\mu$g/mL concentration. The proliferation of mouse spleen cells treated with saponin was increased in a dose-dependent manner compared with untreated control cells until the concentration of 1 $\mu$g/mL but decreased at higher concentrations than that. The NO production in marcrophage cell lines (RAW 264.7) treated with saponin was increased in a dosedependent manner compared with untreated control cells.

Expression and Role of the System L Amino Acid Transporter in FOB Human Osteoblast Cells (사람 골모세포 FOB에서 아미노산 수송계 L의 발현 및 역할)

  • Kim, Chang-Hyun;Park, Joo-Cheol;Kim, Do Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.9
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    • pp.1367-1374
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    • 2005
  • Amino acid transporters play an important role in supplying nutrition to normal and cancer cells for cell proliferation. Amino acid transport system L is a major nutrient transport system responsible for the $Na^+$-independent transport of neutral amino acids including several essential amino acids. The system L is divided into two major subgroups, the L-tyre amino acid transporter 1 (LAT1) and the L-type amino acid transporter 2 (LAT2). In the present study, we have examined the expression and functional characterization of system L amino acid transporters in FOB human osteoblast cells. RT-PCR and western blot analysis have revealed that the FOB cells expressed LAT1, LAT2 together with their associating protein 4F2hc. The uptakes of $[^{14}C]_L$-leucine by FOB cells are $Na^+$-independent and almost completely inhibited by system L amino acid transporter selective inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). These results suggest that the transport of neutral amino acids including several essential amino acids for cellular nutrition into the FOB human osteoblast cells is mediated by system L amino acid transporters.

Antimicrobial synergism of Camellia sinensis-isolated five phenol compounds and R-(-)-carvone against mutans streptococci (다엽의 5가지 페놀성분과 R-(-)-carvone의 치아우식균 Mutans Streptococci에 대한 항균력 상승효과)

  • Song, Ok-Hee;Kang, Ok-Hua;Mun, Su-Hyun;Kim, Min-Chul;Han, Young-Sun;Choi, Sung-Hoon;Lee, Young-Seob;Kwon, Dong-Yeul
    • The Korea Journal of Herbology
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    • v.31 no.5
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    • pp.7-13
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    • 2016
  • Objectives : Camellia sinensis (Theaceae) possesses a various beneficial effects such as free radical-scavenging, inactivation of urokinase in cancer cell proliferation, antibacterial, and hypotensive. Dental caries is one of the most common oral infectious disease in a human. Oral microorganisms play a significant role in the etiology of dental caries. An aberration to this ecology due to dietary habits, improper oral hygiene or systemic factors lead to an increase in cariogenic microorganisms. Cariogenic microorganisms like Streptococcus mutans and Streptococcus sobrinus encourage the accumulation and adherence of plaque biofilm by metabolizing sucrose into glucans. The purpose of this study was to investigate the antimicrobial activity of phenolic compounds of Camellia sinensis and R-carvone, monoterpenes, is can be found naturally in numerous essential oils, on Streptococcus mutans and Streptococcus sobrinus .Methods : The antimicrobial activity of these compounds was determined by the broth microdilution method and checkerboard dilution assay to investigate the potential synergistic effects of each five compounds of Camellia sinensis (C. sinensis) and R-carvone.Results : C. sinensis-isolated compounds and R-carvone were determined with MIC of more than 1,000 ㎍/mL. However, the combination test showed significant synergism against S. mutans and S. sobrinus, implicated in the lowered MICs.Conclusions : These results suggest that combinatory application of phenolic five compounds (theophyllin, l-theanine, epicatechin, epicatechin gallate, and caffeine) from C. sinensis and R-carvone has a potential synergistic effect and thus may be useful as a mouthrinse in helping control cariogenic microorganism.

Inhibition of human breast carcinoma by BLC (Sargassum fulvellum) and BLC/HEN Egg in vitro and in vivo

  • Jo, Eun-Hye;Cho, Sung-Dae;Ahn, Nam-Shik;Jung, Ji-Won;Yang, Se-Ran;Park, Joon-Suk;Hwang, Jae-Woong;Lee, Sung-Hoon;Park, Jung-Ran;Kim, Sun-Jung;Park, Hyun-Kyung;Lee, Yong-Soon;Kang, Kyung-Sun
    • Korean Journal of Veterinary Research
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    • v.45 no.1
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    • pp.85-91
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    • 2005
  • Much of the interest on the chemopreventive properties of herbs and plants has been raised, whereas little is regarding to anti-tumor effect of farming and aquatic products. In the present study, the anti-tumor effect of hot-water extract of a seaweed, BLC (Sargassum fulvellum) and BLC/HEN egg was investigated using MCF-7 cells in vitro and in vivo systems. We found that the BLC extract and BLC/HEN egg inhibited cell proliferation in a dose-dependent manner, which might be mediated through up-regulation of p53. Furthermore, this test compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and down-regulation of a anti-apoptotic Bcl-2 protein, not by immune system. Nude mice bearing established breast tumors (with exogenous estradiol) were treated with BLC extract and BLC/HEN egg. Treatment BLC extract and BLC/HEN egg caused a 42% and 71% inhibition of tumor growth, respectively. Both agents caused a significant inhibition of volume and weight growth of estrogen independent human breast tumors established from MCF-7 cells. Our results suggested that BLC extract and BLC/HEN egg have the efficacious effect of human breast cancer not only in vitro but also in vivo.

Synergistic Effect of Yuza(Citrus junos) Extracts and Ascorbic Acid on Antiproliferation of Human Cancer Cells and Antioxidant Activity (비타민 C가 첨가된 유자 추출물의 항산화능과 암세포 증식억제 상승효과)

  • Shon, Mi-Yae;Park, Seok-Kyu
    • Food Science and Preservation
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    • v.13 no.5
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    • pp.649-654
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    • 2006
  • To enhance beneficial effects of citron fruits, anticancer and antioxidant activities of citron fruits extracts were assessed with or without ascorbic acid. Total phenolic acids and flavonoids of fruits peels and flesh extracts were determined. Fruits peels contained more phenolic acids and flavonoids than those detected in flesh extracts. Scavenging activities of 1,1-diphenyl-2-picrylhydrazyl radicals and reducing powers were increased depending on the concentration. The antioxidant activities on oxidation of linoleic acid emulsion incubated at $50^{\circ}C$ were increased but the effect was small to that of butylated hydroxy toluene and ascorbic acid. The anti-tumorigenic effect of these compounds were investigated. They were shown to inhibit the in vitro proliferation of four human tumorigenic cell lines, HT-29, MCF-7, DU-145 and HepG2, in a doso-dependent manner. This study demonstrated that the antioxidant and anticancer activities of citron fruits extracts were derived from their phenols and flavonoids.

Induction of Apoptosis by Pectenotoxin-2 Isolated from Marine Sponges in U937 Human Leukemic Cells (인체 혈구암세포 U937에서 해양해면동물에서 추출된 Pectenotoxin-2에 의한 Apoptosis의 유발에 관한 연구)

  • Shin, Dong Yeok;Kang, Ho Sung;Bae, Song-Ja;Jung, Jee H.;Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.2
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    • pp.63-70
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    • 2006
  • Natural product compounds are the source of numerous therapeutic agents. The marine environment produces natural products from a variety of structural classes exhibiting activity against numerous disease targets including anticancer agents. Among these, pectenotoxin-2 (PTX-2), which was first identified as a cytotoxic entity in marine sponges, which depolymerizes actin filaments, was found to be highly effective and more potent to activate an intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those with functional p53 both in vitro and in vivo. However, the anti-proliferative mechanism of the compound at non-cytotoxic concentrations has not yet been explored. In the current study, we sought to investigate anti-proliferation and apoptosis of PTX-2 against U937 human leukemic cells and its underlying molecular mechanism. Exposure of U937 cells to PTX-2 resulted in growth inhibition and induction of apoptosis in dose- and time-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. The anti-proliferative effect of PTX-2 was associated with a marked increase in the expression of cyclin-dependent kinase p21 (WAF1/CIP1) mRNA which was tumor suppressor p53-independent. The increase in apoptosis was connected with a time-dependent down-regulation of anti-apoptotic Bcl-XL and inhibitor of apoptosis proteins (IAPs) family such as XIAP and cIAP-2. Though additional studies are needed, these findings suggested that PTX-2-induced inhibition of U937 cells was associated with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of PTX-2.

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