• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8539-8548
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• 2014

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK($p38{\alpha}$, $p38{\beta}$, $p38{\gamma}$ and $p38{\delta}$), and ERK3/ERK4/ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Several components of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK, ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK) pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.237-246
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• 2005

Background: Little information is available on the identification and characterization of the upstream regulators of the signal transduction cascades for Mycobacterium tuberculosis (M. tbc)-induced ERK 1/2 activation and chemokine expression. We investigated the signaling mechanisms involved in expression of CCL3 /MIP-1 and CCL4/MIP-1 in human primary monocytes infected with M. tbc. Methods: MAP kinase phosphorylation was determined using western blot analysis with specific primary antibodies (ERK 1/2, and phospho-ERK1/2), and the upstream signaling pathways were further investigated using specific inhibitors. Results: An avirulent strain, M. tbc H37Ra, induced greater and more sustained ERK 1/2 phosphorylation, and higher CCL3 and CCL4 production, than did M. tbc H37Rv. Specific inhibitors for mitogen-activated protein kinase (MAPK) kinase (MEK; U0126 and PD98059) significantly inhibited the expression of CCL3 and CCL4 in human monocytes. Mycobactetia-mediated expression of CCL3 and CCL4 was not inhibited by the Ras inhibitor manumycin A or the Raf-1 inhibitor GW 5074. On the other hand, phospholipase C (PLC) inhibitor (U73122) and protein kinase C (PKC)specific inhibitors ($G\ddot{o}6976$ and Ro31-8220) significantly reduced M. tbc-induced activation of ERK 1/2 and chemokine synthesis. Conclusion: These results are the first to demonstrate that the PLC-PKC-MEK-ERK, not the Ras-Raf-MEK-ERK, pathway is the major signaling pathway inducing M. tbc-mediated CCL3 and CCL4 expression in human primary monocytes.

• BMB Reports
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• v.44 no.7
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• pp.452-457
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• 2011

The Egr-1 is an immediate early response gene encoding a transcription factor that functions in the regulation of cell growth, differentiation, and apoptosis. Estrogen has diverse physiological effects, including cellular proliferation and neuroprotection against brain injury. There are two types of estrogen receptors (ERs), $ER{\alpha}$ and $ER{\beta}$. $ER{\alpha}$-induced Egr-1 expression has been extensively studied; however, the role of $ER{\beta}$ is yet not known. In the present study, we investigated whether or not $ER{\beta}$ induces Egr-1 expression in C6 rat glioma cells, which express $ER{\beta}$ but not $ER{\alpha}$. Our results show that $ER{\beta}$ promoted up-regulation of Egr-1 expression via a non-genomic mechanism involving the Raf/MEK1/Erk/Elk-1 signaling cascade.

• Journal of Oral Medicine and Pain
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• v.26 no.2
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• pp.95-105
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• 2001

제 4형 콜라젠을 분해하는 MMP-9은 조직 재생에 중요한 역할을 하기 때문에 주목받아 왔는데, 이전의 문헌들에서 PMA에 의해 이 유전자 발현이 강하게 상승발현된다고 알려져 있다. 비록 MMP-9 발현을 조절하는 PMA의 기전이 잘 밝혀지지는 않았지만, 다른 유전자발현에서의 이 phorbol ester의 효과는 c-raf-1-ERK 신호전달통로의 활성에 관해 연구되어 오고 있다. 하지만 이번 연구에서 저자는 MMP-9 발현에서 PMA의 상승효과에는 대개는 스트레스성 자극과 관련된 JNK1 의존성 신호전달과정이 또한 필요하다는 다른 가능성을 조사하였다. 그 결과 JNK 억제재중 하나인 SP 600125가 UM-SCC-1세포주에서 PMA에 의해 유도된 MMP-9 상승발현을 용량의존적으로 억제하는 것으로 나타났고 72시간동안 전처치를 한 경우에 그의 억제효과가 최대이었다. phorbol ester로 처리한 세포에 GAL4 luciferase reporter와 vector를 주입해서 조사한 결과 PMA가 c-Jun transacting 활성을 상승시켰다. 그뿐 아니라 PMA에 의한 MMP-9 촉진자 활성에는 AP-1 motif가 필요하며 이 motif에 c-Jun이 결합하는 것을 EMSA를 통해 확인하였다. 결론적으로 UM-SCC-1 세포주에서 PMA에 의한 MMP9의 증가된 발현은 이미 밝혀진 ERK 경로뿐 아니라 JNK 경로를 통한 결과임이 밝혀져 이 경로를 차단하는 방법이 또하나의 암치료 방향을 제시해주고 있다.

• Korean Journal of Organic Agriculture
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• v.21 no.1
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• pp.105-113
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• 2013

Antibacterial activity is an important feature for the development of antibiotics alternatives. Plant extract is considered as a promising alternative for organic farming. In this study, a total of 11 plants were extracted using ethanol to determine their antibacterial activities against to Staphylococcus aureus, Listeria monocytogens, Mannheimia haemolytica and Salmonella gallinarum. The synergistic interaction among plant extracts was also investigated. Plants used in this study were Carthamus nctoricus L. (pA), Poncirus trifollata Raf. (pB), Scutellaria balcalensis Georgi (pC) Prunus sargentii (pD), Cucurbita moschata $D_{UCH}$ Leaf (pE), Allium cepa L. peel (pF) Portulaca oleracea L. (pG), Xanthium strumarium L. (pH), Duchesnea chrysantha (pI), Cudrania tricuspidata (pJ) and Juniperus chinensis L. (pK). The pB and pA had the most broad antibacterial spectrum and the highest activity against to Staph. aureus among plant extract, respectively. In the synergistic interaction, the mixtures of pA and pC as well as pA and pF had batter antibacterial activity against to Staph. Aureus compared with other mixtures.

• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.138-143
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• 2011

A high performance liquid chromatography (HPLC) method was developed for simultaneous determination of two major flavonoid glycosides (poncirin and nanringin) in Poncirus trifoliata Raf. by different harvesting times and locations for two years. A SunFire $C_{18}$ column (4.6 mm${\times}$250 mm, 5 ${\mu}M$) was used at $40^{\circ}C$ for the determination of poncirin and naringin. The mobile phase using gradient flow consisted of two solvent systems. Solvent A was 1.0% (v/v) aqueous acetic acid and solvent B was acetonitrile with 1.0% (v/v) acetic acid. Flow rate was 1.0 mL/min and injection volume was 10 ${\mu}l$. The chromatogram was monitored by photodiode array (PDA) detection at 280 nm for the identification of two flavonoid glycosides in P. trifoliata. The contents of the two components in P. trifoliata ranged from 0.32~13.02%.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• Korean Journal of Plant Resources
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• v.31 no.6
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• pp.684-694
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• 2018

This study describes the successful establishment of a cryopreservation protocol for Citrus limon cultivars: 'Frost Eureka limon' and 'Cook Eureka limon', using a droplet-vitrification method. The shoot tips that were excised from in vitro grown seedlings of the two cultivars were preserved in liquid nitrogen (LN) and successfully regenerated into whole plants. Excised shoot tips were pre-cultured for 1 or 2 days in 0.3 M and 0.5 M sucrose solutions at $25^{\circ}C$ and incubated in a loading solution (LS) composed of 17.5% glycerol + 17.5% sucrose in Murashige and Skoog (MS) medium for 40 min at $25^{\circ}C$. Prior to direct immersion in LN for 1 h, the shoot tips were dehydrated with plant vitrification solution 2 (PVS2) at $0^{\circ}C$ or PVS3 at $25^{\circ}C$. The frozen shoot tips were re-warmed and unloaded with 1.2 M sucrose in $\text\tiny{^1/_2}$ MS for 30 min at $25^{\circ}C$. Shoot tips were post-cultured overnight on survival medium and then micrografted onto 'trifoliate orange' (Poncirus trifoliate (L.) Raf. seedling rootstocks for recovery and to produce whole plants. The highest regrowth rates were 53.5% and 50.3% for cryopreserved shoot tips of 'Frost Eureka limon' and 'Cook Eureka limon', respectively, when pre-cultured in 0.3 M and 0.5 M sucrose concentrations in a sequencing manner, with LS and treated with PVS2 for 60 min at $0^{\circ}C$. We also investigated whether the ammonium ion concentration on post-culture medium affected the viability of the cryopreserved Citrus shoot tips. The viability of cooled samples, following culturing on woody plant media (WPM) containing $\text\tiny{^1/_4}$ ammonium nitrate overnight before micrografting, was the highest (70.3%) in 'Frost Eureka limon'. The study described here is a cost-effective and safe method to conserve Citrus fruit cultivars, for the improvement and large-scale multiplication of fruit plants and for breeding disease resistance.

• Herbal Formula Science
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• v.15 no.2
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• pp.127-137
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• 2007

The purpose of this study was to investigate the effect of Yong-dam-sa-gan-tang (YST) on apoptosis in HepG2 cells, First of all. to study the cytotoxic effect of methanol extract of YST on HepG2 cells, the cells were treated with various concentrations of YST and then cell viability was determined by XTT reduction method and trypan blue exclusion assay. YST reduced proliferation of HepG2 cells in a dose-dependent manner. To confirm the induction of apoptosis, HepG2 cells were treated with various concentrations of YST. The cleavage of poly AD P-ribose polymerase (P ARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of caspase-3, procaspase-8 and procaspase-8 were examined by western blot analysis. YST decreased procaspase-3, procaspase-8 and procaspase-9 levels in a dose-dependent manner and induced the clevage of PARP. YST triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome c from mitochondria to cytosol. Furthermore, YST also downregulated the anti-apoptotic Bcl-2 and upregulated the pro-apoptotic-Bax. Therefore, this result suggest that YST induced HepG2 cell death through the mitochondrial pathway. Sustained activation of the Ras/Raf/MEK/ERK cascade in cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. YST decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. These results suggest that YST is potentially useful as a chemo-therapeutic agent in HepG2.

• Food Science and Biotechnology
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• v.14 no.4
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• pp.498-502
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• 2005

Three Korean soybean varieties - Shinpaldal-2, Seomoktae and Seoritae - were investigated for changes in their physical properties and the amount of functional components (i.e. isoflavones and oligosaccharides), during germination. Soybeans were germinated at $20^{\circ}C$ for 96 hr in complete darkness. The dry weights of cotyledone, hypocotyl, seed coat, and hilum of Seoritae were heavier than those of other varieties. The dry weights of the three bean varieties decreased steadily in spite of root growth. The largest amount of isoflavone content was observed from Shinpaldal-2 (1.824 mg/g), followed by Seoritae (1.216 mg/g) and Seomoktae (1.125 mg/g). Total isoflavone content increased by 13% during initial germination, and then decreased thereafter. Aglycone types such as daidzein and genistein dominated the increase in isoflavone contents. The increase in genistein content of Shinpaldal-2 was 17.5 fold compared with ungerminated soybean, while the amount of daidzein was 6.7 times as much as ungerminated Shinpaldal-2 over an 18-hr germination period. Oligosaccharide contents such as raffinose (Raf) and stachyose (Sta) rapidly decreased during germination, while the sucrose (Sue) content remained constant until 36-48 hr of germination. From these results, it was clearly shown that the germination process significantly changed the contents of functional nutrients in soybeans. Therefore, the optimization of germination process should be considered to improve the biological functionality of soybeans in food processing.