• Title/Summary/Keyword: anti-proliferative effects

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Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells

  • Tudev, Munkhtsetseg;Lim, Yong;Park, Eun-Seok;Kim, Won-Sik;Lim, Il-Ho;Kwak, Jae-Hwan;Jung, Jae-Kyung;Hong, Jin-Tae;Yoo, Hwan-Soo;Lee, Mi-Yea;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.187-194
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    • 2011
  • Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Immunomodulatory Effects of Cimicifugae Rhizoma Extracts in Macrophages

  • Pyo, Suh-Kneung;Kim, Byung-Oh;Choi, Hye-Sook;Son, Eun-Wha
    • Preventive Nutrition and Food Science
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    • v.11 no.4
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    • pp.268-272
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    • 2006
  • Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE ($1\sim50\;{\mu}g/mL$) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.

Inhibitory Effect on the Lipopolysaccharide-Induced Nitric Oxide Formation in RAW264.7 and on the Proliferation of HeLa Cell Lines by the Stem Bark Extracts of Abies nephrolepis (분비나무 줄기 수피 추출물에 의한 HeLa Cell Line의 증식억제 효과와 RAW264.7 세포에서 Lipopolysaccharide에 의해 유도된 Nitric Oxide 생성 저해효과)

  • Bae, Ki-Eun;Chong, Han-Soo;Kim, Dong-Sup;Choi, Young-Woong;Kim, Yeung-Suk;Kim, Young-Kyoon
    • Korean Journal of Pharmacognosy
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    • v.40 no.1
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    • pp.77-81
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    • 2009
  • Abies nephrolepis(Pinaceae) extracts were tested for determined immune system regulating activity based on antiinflammatory activity, antioxidant activity and anti-proliferative effect on HeLa cell line. The A. nephrolepis extracts increased dose-dependently anti-proliferation of HeLa cell line. The DM fraction of the extracts having anti-proliferatative effects of HeLa cell line was fractionalized four subfractions($D1{\sim}D4$). Inflammation-induced NO production was inhibited by D2 and D4 in LPS-activated RAW264.7 macrophages. And also, this fractions showed antioxidant activity examined by DPPH radical scavenging effects. These results suggest that the potential use of DM fraction of A. nephrolepis in chemoprevention and regulation overproduction of NO on pathogenic conditions. The mechanism of the inflammatory effects, however, must be evaluated through various parameters in the induction cascade of NO production.

Antioxidant, Tyrosinase Inhibitory, and Anti-proliferative Activities of Gochujang Added with Cheonggukjang Powder Made from Sword Bean (작두콩 청국장 첨가 고추장의 항산화, tyrosinase 저해 및 암세포 증식 억제 효과)

  • Chang, Moon-Ik;Kim, Jae-Young;Kim, Un-Sung;Baek, Seung-Hwa
    • Korean Journal of Food Science and Technology
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    • v.45 no.2
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    • pp.221-226
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    • 2013
  • This study aimed to examine the antioxidant, tyrosinase inhibitory, and anti-proliferative activities (A549, G361, HT-29, and MDA-MB-231) of fermented gochujang (made from sword bean cheonggukjang powder (SBC) for 90 days. Gochujang was prepared by adding 0 (SBC 0), 2 (SBC 2), 5 (SBC 5), 8 (SBC 8) and 10% (SBC 10) levels with SBC, and all experiments were measured at diluted levels of 20, 50 and 100 times. The antioxidant activity and tyrosinase inhibitory effect demonstrated that SBC 10 increased approximately 1.2 and 1.1 times compared with SBC 0, respectively, at diluted levels of 50 and 100 times. The anti-proliferative effects of A549, G361, and HT-29 presented that SBC 10 were 2.8, 1.1, and 8.9 times higher compared with SBC 0, respectively, at diluted levels of 50, 20, and 100 times. In the case of MDA-MB-231, SBC 10 was 3.7 times higher compared with SBC 5 at diluted level of 20 times. As a result, we confirmed that SBC gochujang was improved for physiological activities and anti-proliferative effects.

Preventive Effects of a Major Component of Green Tea, Epigallocathechin-3-Gallate, on Hepatitis-B Virus DNA Replication

  • Karamese, Murat;Aydogdu, Sabiha;Karamese, Selina Aksak;Altoparlak, Ulku;Gundogdu, Cemal
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4199-4202
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    • 2015
  • Background: Hepatitis B virus infection is one of the major world health problems. Epigallocatechin-3 gallate is the major component of the polyphenolic fraction of green tea and it has an anti-viral, anti-mutagenic, anti-tumorigenic, anti-angiogenic, anti-proliferative, and/or pro-apoptotic effects on mammalian cells. In this study, our aim was to investigate the inhibition of HBV replication by epigallocatechin-3 gallate in the Hep3B2.1-7 hepatocellular carcinoma cell line. Materials and Methods: HBV-replicating Hep3B2.1-7 cells were used to investigate the preventive effects of epigallocatechin-3 gallate on HBV DNA replication. The expression levels of HBsAg and HBeAg were determined using ELISA. Quantitative real-time-PCR was applied for the determination of the expression level of HBV DNA. Results: Cytotoxicity of epigallocathechin-3-gallate was not observed in the hepatic carcinoma cell line when the dose was lower than $100{\mu}M$. The ELISA method demonstrated that epigallocatechin-3 gallate have strong effects on HBsAg and HBeAg levels. Also it was detected by real-time PCR that epigallocatechin-3 gallate could prevent HBV DNA replication. Conclusions: The obtained data pointed out that although the exact mechanism of HBV DNA replication and related diseases remains unclear, epigallocatechin-3 gallate has a potential as an effective anti-HBV agent with low toxicity.

Mistletoe Lectin (Viscum album coloratum) Modulates Proliferation and Cytokine Expressions in Murine Splenocytes

  • Lyu, Su-Yun;Park, Won-Bong
    • BMB Reports
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    • v.39 no.6
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    • pp.662-670
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    • 2006
  • It is well documented that an extract of European mistletoe has a variety of biological effects, such as the stimulation of cytokine production from immune cells, and additional immunoadjuvant activities. While the European mistletoe has been studied intensively, we know less about Korean mistletoe as a therapeutic plant, especially as a possible immunomodulating drug. This study will investigated the effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) on murine splenocytes to investigate whether VCA acts as an immunomodulator, which could lead to improved immune responses in these cells. The results showed that VCA inhibited cell proliferation at higher concentrations (at 1-8 ng/ml) and enhanced cell proliferation at lower concentrations (at 4-32 pg/ml). Further studies were carried out to determine if the pro-proliferative or anti-proliferative activity exhibited by VCA was correlated with cytokine secretion. Consequently, interferon (IFN)-$\gamma$ secretion was decreased in concanavalin A (ConA)-stimulated murine splenocytes by VCA (4-64 ng/ml), but there was no change in IL-4 levels. This suggests that VCA has the ability to modulate murine splenocyte proliferation and can possibly act on the balance of Th1/Th2 cellular immune responses.

Component Analysis and Anti-Proliferative Effects of Ethanol Extracts of Fruits, Leaves, and Stems from Elaeagnus umbellata in HepG2 Cells (보리수나무 열매, 잎 및 줄기 에탄올 추출물의 함유성분 분석과 간암 세포 증식억제 효과)

  • Kim, Min-Ju;Lim, Jong-Soon;Yang, Seun-Ah
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.6
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    • pp.828-834
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    • 2016
  • The aim of this study was to evaluate the physicochemical properties and antioxidant and anti-proliferative activities of different plant parts of Elaeagnus umbellata Thunb. extracted with ethanol (EtOH). EtOH extract of stems presenting the highest content of polyphenols showed the strongest 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity ($EC_{50}=54.04{\mu}g/mL$). The total content of free amino acids decreased in the order of leaves (6,179.12 mg/100 g)> stems (1,211.69 mg/100 g)> fruits EtOH extract (378.88 mg/100 g), and asparagine (1,907.57 mg/100 g), ${\gamma}-aminobutyric$ acid (300.17 mg/100 g), and proline (233.48 mg/100 g) were the major free amino acid in leaves, stems, and fruits, respectively. Five phenolic compounds in each extract were measured by using liquid chromatography- tandem mass spectrometry, and gallic acid (98.95 mg/100 g) and (+)-catechin (1,575.99 mg/100 g) were present as major components in leaves and stems, respectively. EtOH extract of leaves showed the highest anti-proliferative activity against HepG2 cells as measured by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazoliumbromide and lactate dehydrogenase assay but had no effects on Chang liver cells.

Anti-inflammatory and Cellular Proliferation Effects of Ethanol Extracts from 5 Kinds of Oriental Medical Plants (5종의 한약재 에탄올 추출물의 항염증 및 표피세포 증식 활성)

  • Jung, Min-Hwa
    • Journal of Life Science
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    • v.28 no.9
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    • pp.1022-1029
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    • 2018
  • This study was carried out to search for the anti-inflammatory activities of ethanol extracts obtained from 5 kinds of oriental medical plant; Pleuropterus multiflorus extract (PME), Acorus calamus L. extract (ACE), Lithospermum erythrorhizon Siebold & Zucc. extract (LEE), Xanthium strumarium L. extract (XSE), Lonicera japonica extract (LJE), which have traditionally been used as a drug in oriental medical plants in Korea. XSE showed cytotoxicity at 100, $200{\mu}g/ml$ concentration in RAW264.7 cells (p<0.05) and ACE showed cytotoxicity at $200{\mu}g/ml$ concentration in RAW264.7 cells (p<0.05). But other oriental medical plants did not showed cytotoxicity was observed in RAW264.7 cells below $200{\mu}g/ml$ concentration. These extracts at non-toxic concentrations showed anti-inflammatory effects. PME, ACE, XSE and LJE showed a concentration-dependent inhibitory effect on NO production and $PGE_2$ production in LPS-induced RAW264.7 cells. In particular, XSE showed the highest NO production inhibition ($52.9{\mu}g/ml$, $IC_{50}$) as well as the highest $PGE_2$ production inhibition at $50{\mu}g/ml$ (73.6%). ACE and LEE showed cell proliferation effects on HaCaT keratinocyte cells. Especially, LEE showed 21.1, 53.5 and 99.6% proliferative activity by incubation for 1, 3, 5days at $100{\mu}g/ml$ concentration. ACE also showed 11.2, 26.0% proliferative activity for 1day and 3days at $10{\mu}g/ml$ concentration. As a result of this study, ethanol extracts obtained from 5 kinds of oriental medical plant showed anti-inflammatory activity and HaCaT cell regeneration effect.

Antioxidative Effects and Anti-proliferative Effects of MeOH, BuOH and Ethyl Acetate Fractionated from Stephania delavayi Diels (일문전(Stephania delavayi Diels.) 메탄올, 부탄올, 에틸아세테이트 분획물의 항산화 및 세포증식억제 효과)

  • Li, Yong-Chun;Kim, Kyoung-Hee;Xu, Hong-De;Park, Dae-Hun;Choi, Yeon-Shik;Hwang, Hye-Rim;Lee, Min-Jae;Choi, Jong-Jin;Kwon, Myung-Sang;Yook, Hong-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.3
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    • pp.297-301
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    • 2009
  • Stephania delavayi Diels. (S. delavayi Diels.) has been used as a drug for pain-relieving and acute gastroenteritis treatment in China. Because the major therapeutic mechanism of anti-inflammatory drug is to inhibit the cyclooxygenase (COX)-2 and because COX-2 proteins inhibit apoptosis, COX-2 inhibitor has been thought as the anticancer drug candidate. For this reason, we examined S. delavayi Diels. as an anticancer drug. S. delavayi Diels. was fractionated with methanol and then partitioned with ethyl acetate, n-butanol and water. The antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and reducing power. DPPH radical scavenging activities of the crude fractions at the concentration of $1,000{\mu}g/mL$ were 75.23% (n-butanol), 68.11% (methanol), 63.58% (ethyl acetate), and 50.13% (water). The reducing power increased according to the concentration in dose-dependent manner. Also, when the antiproliferation effects of each fraction against human breast cancer cell-lines MDA-MB-231 and MCF-7 were examined, methanol extract, n-butanol fraction and ethyl acetate fraction exhibited cell proliferative inhibition effects in both cell-lines whereas water fraction did not. Among the crude fractions, the n-butanol fraction exhibited the most potent anti-proliferation effect. In conclusion, fractions from S. delavayi Diels. are promising anticancer drug candidates.