• Title/Summary/Keyword: p53 activation

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Effects of Triterpenoids from Luvunga scandens on Cytotoxic, Cell Cycle Arrest and Gene Expressions in MCF-7 Cells

  • Taher, Muhammad;Al-Zikri, Putri Nur Hidayah;Susanti, Deny;Arief Ichwan, Solachuddin Jauhari;Rezali, Mohamad Fazlin
    • Natural Product Sciences
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    • v.22 no.4
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    • pp.293-298
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    • 2016
  • Plant-derived triterpenoids commonly possesses biological properties such as anti-inflammatory, antimicrobial, anti-viral and anti-cancer. Luvunga scandens is one of the plant that produced triterpenoids. The aims of the study was to analyze cell cycle profile and to determine the expression of p53 unregulated modulator of apoptosis (PUMA), caspase-8 and caspase-9 genes at mRNA level in MCF-7 cell line treated with two triterpenoids, flindissol (1) and 3-oxotirucalla-7,24-dien-21-oic-acid (2) isolated from L. scandens. The compounds were tested for cell cycle analysis using flow cytometer and mRNA expression level using quantitative RT-PCR. The number of MCF-7 cells population which distributed in Sub G1 phase after treated with compound 1 and 2 were 7.7 and 9.3% respectively. The evaluation of the expression of genes showed that both compounds exhibited high level of expression of PUMA, caspase-8 and caspase-9 as normalized to ${\beta}-actin$ via activation of those genes. In summary, the isolated compounds of L. scandens plant showed promising anticancer properties in MCF-7 cell lines.

c-Src Antisense Complexed with PAMAM Denderimes Decreases of c-Src Expression and EGFR-Dependent Downstream Genes in the Human HT-29 Colon Cancer Cell Line

  • Nourazarian, Ali Reza;Pashaei-Asl, Roghiyeh;Omidi, Yadollah;Najar, Ahmad Gholamhoseinian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2235-2240
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    • 2012
  • c-Src is one member of non-receptor tyrosine kinase protein family that has over expression and activation in many human cancer cells. It has been shown that c-Src is implicated in various downstream signaling pathways associated with EGFR-dependent signaling such as MAPK and STAT5 pathways. Transactivation of EGFR by c-Src is more effective than EGFR ligands. To inhibit the c-Src expression, we used c-Src antisense oligonucleotide complexed with PAMAM Denderimes. The effect of c-Src antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay. Then, the expression of c-Src, EGFR and the genes related to EGFR-depended signaling with P53 was applied by real time PCR. We used western blot analysis to elucidate the effect of antisense on the level of c-Src protein expression. The results showed, c-Src antisense complexed with PAMAM denderimers has an effective role in decrease of c-Src expression and EGFR-dependent downstream genes.

Water-Soluble Fraction of Rheum Undulatum Attenuates $Amyloid-\beta-induced$ Neuronal Death and Microglial Activation in Vitro

  • Jung Bo Mi;Kim Sung Ok;Yun Su Jin;Hwang Eun Joo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.1073-1077
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    • 2005
  • Oxidative stressand glia-associated chronic inflammation have been linked to the pathophysiology of Alzheimer's disease. Rhei rhizoma has been commonly used as a purgative and a haemostatic agent in traditional oriental medicine. Recently, the methanol extract from a dried root of Rheum undulatumhas been shown to have anti-allergic and anti-inflammatory effects. In this study, we tested the potential of the extract of Rheum undulatum for neuroprotective agent. The aqueous extract of Rheum undulatum reduced cell death and p53 phosphorylation in neuronal cells and attenuated levels of cyclooxygenase-2 and inducible nitric oxide synthase mRNAs in BV2 microglial cells treated with $amyloid-\beta$

Autophagy: Noble target mechanisms in natural medicines as anticancer agents (자가식세포작용: 천연물항암제로서의 신규작용기전)

  • Kang, Se-Chan
    • Journal of Plant Biotechnology
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    • v.37 no.1
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    • pp.57-66
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    • 2010
  • Programmed cell death systems are important for an active type of cell deaths. Among them, a type of programmed cell death, autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Thus, in the area of cancer, over the time frame form around the 1940s to date, of the 155 small molecules, 73% are other than "synthetic", with 47% actually being either "natural products" or "directly derived therefrom". Autophagy has multiple physiological functions in multicellular organisms, including protein degradation and organelle turnover. Genes and proteins that constitute the basic machinery of the autophagic process were first identified in the yeast system and some of their mammalian orthologues have been characterized as well. Numerous oncogenes, including Akt1, Bcl-2, NF1, PDPK1, class I PI3K, PTEN, and Ras and oncosuppressors, inculuding Bec-1, Bif-1, DAPK-1, p53 and UVRAG suppress or promote the autophagy pathway. Regulation of autophagy in tumors is governed by similar principles of the normal cells, only in a much more complicated manner, given the frequently observed abnormal PI3K activation in cancer and the multitude of interactions between the PI3K/AKT/mTOR pathway and other cell signaling cascades, often also deregulated in tumor cells. Autophagy induction by some anticancer agents underlines the potential utility of its induction as a new cancer treatment modality of development for natural medicines.

A Study on the Spatial Organization of Outpatient Department in General Hospital - Focused on the Latest Planned General Hospital of Scale more than 500 Beds - (종합병원 외래진료부의 공간구성과 규모계획에 관한 조사연구 - 최근 계획된 500병상 이상 규모의 종합병원을 중심으로 -)

  • Son, Jae-Won;Lee, Teuk-Koo
    • Journal of The Korea Institute of Healthcare Architecture
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    • v.13 no.2
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    • pp.53-60
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    • 2007
  • Various changes in medical environments including growing elderly population, chronic diseases, deepening competition among hospitals since opening to foreign medical service, economic strategy for improvement of profit system have caused hospitals to be specialized. In this backgrounds, the purpose of this study is to receive basic data for architectural planning on the spatial organization of outpatient department in general hospital. The results of this study were as follows; First, major changes of outpatient department in general hospital are composed of 'co-work in medical examination and treatment', 'decentralization of diagnosis and treatment(D/T)' and 'patient-oriented medical service'. Changes by co-work system include appearance of medical offices for co-work, activation of specialized clinics, grouping of E/T section for outpatient and various types of specialized centers. Second, the grouping of E/T sections means the modification of E/T system and organization in general hospitals, and a new spatial organization will be needed. Third, the types of specialized centers are getting varied. they are classified into several types including disease-resource, social stratum-resource, human organ-resource, health-resource, rehabilitation-resource, alternative medical center and so on.

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[ ${\alpha}$ ]Synuclein Induces Unfolded Protein Response Via Distinct Signaling Pathway Independent of ER-membrane Kinases

  • Kang, Shin-Jung;Shin, Ki-Soon;Kim Kwon, Yun-Hee
    • Animal cells and systems
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    • v.10 no.3
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    • pp.115-120
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    • 2006
  • Parkinson's disease (PD) is a neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Mutations in ${\alpha}$-synuclein have been causally linked to the pathogenesis of hereditary PD. In addition, it is a major component of Lewy body found in the brains of sporadic cases as well. In the present study, we examined whether overexpression of wild type or PD-related mutant ${\alpha}$-synuclein induces unfolded protein response (UPR) and triggers the known signaling pathway of the resulting endoplasmic reticulum (ER) stress in SH-SY5Y cells. Overexpression of wild type, A30P, and A53T ${\alpha}$-synuclein all induced XBP-1 mRNA splicing, one of the late stage UPR events. However, activation of ER membrane kinases and upregulation of ER or cytoplsmic chaperones were not detected when ${\alpha}$-synuclein was overexpressed. However, basal level of cytoplsmic calcium was elevated in ${\alpha}$-synuclein-expressing cells. Our observation suggests that overexpression of ${\alpha}$-synuclein induces UPR independent of the known ER membrane kinase-mediated signaling pathway and induces ER stress by disturbing calcium homeostasis.

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

  • Yeo, Hyunjin;Lee, Jeong Yeon;Kim, JuHwan;Ahn, Sung Shin;Jeong, Jeong You;Choi, Ji Hye;Lee, Young Han;Shin, Soon Young
    • BMB Reports
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    • v.53 no.6
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    • pp.323-328
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    • 2020
  • Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

Preparation and Characterization of Watermelon Wine (수박을 이용한 와인의 제조 및 특성)

  • Park, Chan-Sung;Kim, Mi-Lim
    • Food Science and Preservation
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    • v.17 no.4
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    • pp.547-554
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    • 2010
  • We developed watermelon (Citrullus vulgaris Schrad) wine to increase the market for the fruit, which is currently sold only in fresh form. The pH of watermelon wine was pH 2.8~3.4, the total acid level 0.48~0.55%, and the soluble solid $5{\sim}6^{\circ}brix$ alcohol content was 9.5~10.5%. Fermentation of watermelon juice was satisfactory at both 20C and 25C. All of citric acid, malic acid, and oxalic acid were detected in watermelon wine citric acid was the most abundant. All of glucose, fructose, sucrose, and maltose were present in juice, and both fructose and glucose were used in fermentation. Electron-donating ability (EDA) was high, being 80% of the control value when watermelon wine was diluted to $400\;{\mu}l/ml$. SOD-like activities were present in both watermelon juice and wine, being 55.2% and 49.2% of control values, respectively. Nitrite-scavenging ability (NSA) was 70.2% and 53.2% of control values in undiluted juice and wine, respectively. Watermelon juice showed higher activation than did wine, but functionality neither fell nor rose after fermentation. In sensory evaluation of wine, the overall score was better than average, at 4.15, thus establishing the commercial potential of watermelon wine.

Inhibition Effect of Cell Proliferation and Apoptosis by Inonotus obliquus in Human Glioblastoma U-87 MG Cells (차가버섯 추출물에 의한 신경교모세포종 U-87 MG 세포의 증식 억제 효과)

  • Shin, Jung-A;Park, Joo Hyun;Kim, Sun Hee;Song, Kwan Yong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.7
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    • pp.1022-1028
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    • 2013
  • Chaga mushroom (Inonotus obliquus) was considered a functional food with an anti-cancer effect in colon, gastric, and lung cancer. Therefore, this study was conducted in order to elucidate the effect of chaga mushroom extract in brain cancer. Glioblastoma U-87 MG cells were used in investigation of cell survivability, apoptosis, and cell cycle arrest analysis. Treatment with various concentrations of chaga mushroom extract resulted in inhibition of cell proliferation and cell cycle arrest. Although caspase-3 expression was increased over $100{\mu}g/mL$ of chaga mushroom extract treatment, apoptosis factors with Bcl-2, Bax and p53 did not change. In analysis of cell cycle regulatory factors, expression of cyclin D1 and CDK2 decreased in a dose-dependent manner. We have demonstrated the anti-cancer effect of chaga mushroom extract in glioblastoma, which may be mediated by activation of the caspase pathway and induction of cell cycle arrest.

Induction of Apoptosis by Methanol Extract of Endlicheria anomala in Human Lung and Liver Cancer Cells (Endlicheria anomala 메탄올 추출물에 의한 인체 폐암세포주와 간암세포주의 자가사멸 유도)

  • Park, Hyun-jin;Jin, Soojung;Oh, You Na;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.25 no.4
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    • pp.441-449
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    • 2015
  • Endlicheria anomala, a neotropical plant, is found in northern South America and the Amazon region. It is traditionally used to remove poisons and cure gangrene. According to recent data, this plant has diverse biological properties such as anti-oxidative, anti-inflammatory and anti-melanogenic properties. However, the anti-cancer effect of E. anomala and its molecular mechanisms remain unclear. In this study, we examined the anti-cancer effect and the active mechanism of methanol extract of E. anomala (MEEA) in human lung adenocarcinoma cells (A549) and human liver cancer cells (HepG2). Our data revealed that MEEA showed cytotoxic activity in a dose-dependent manner and induced apoptosis both in A549 and HepG2 cells. We verified evidences of apoptosis via formation of chromatin condensation, apoptotic body and accumulation of cells in the subG1 phase. Following observed apoptosis-related phenomena, we found that the induction of apoptosis by MEEA was associated with the increase of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. Furthermore, MEEA-induced apoptosis was characterized with proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of pro-apoptotic Bax expression. Taken together, these findings indicate that MEEA may have potential cancer therapeutic utility in A549 and HepG2 cells.