• Title/Summary/Keyword: Cell proliferation and growth

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Induction of Apoptosis and Inhibition of Growth in Human Gastric Cancer by Piperine (Piperine에 의한 위암세포 AGS 증식 억제와 Apoptosis 유도)

  • Shin, Seong-Ah;Lee, Hae-Nim;Choo, Gang-Sik;Kim, So-Jung;Kim, Hyeong-Jin;Park, Young-Seok;Park, Byung-Kwon;Kim, Byeong-Soo;Kim, Sang-Ki;Lee, Hu-Jang;Jung, Ji-Youn
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1589-1594
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    • 2016
  • Piperine [(E,E)-5-(3,4-methtylenedioxyphenyl)-2,4-pentadienolypiperidide] is a principal of Piperaceae, including Piper nigrum L. and Piper longum Linn., which has been used as a spice and traditional medicine. In this study, we investigated whether or not piperine has anti-cancer effects on AGS human gastric cancer cells. The results demonstrated that piperine not only inhibited proliferation using MTT assay but also induced apoptotic bodies using DAPI assay in a dose-dependent manner in response to piperine. Expression levels of p53, Bax (pro-apoptotic), cleaved caspase-9, and cleaved-PARP increased, whereas expression levels of Bcl-2, XIAP (anti-apoptotic), and Akt decreased in a dose-dependent manner compared with the control by western blotting analysis. To identify the connection between phospo-Akt and Bcl-2 family in response to piperine, LY249002 (Akt inhibitor) was treated with piperine ($150{\mu}M$). The results were shown that expression of phospo-Akt was reduced whereas expression of Bax and cleaved-PARP increased in a dose-dependent manner. These results indicate that piperine induced apoptosis in AGS cells and may serve as a chemopreventive or therapeutic agent for human gastric cancer.

Potentials of Synbiotics for Pediatric Nutrition and Baby Food Applications: A Review (소아 영양 및 유아식 응용을 위한 신바이오틱스의 잠재력: 총설)

  • Jung, Hoo Kil;Kim, Sun Jin;Seok, Min Jeong;Cha, Hyun Ah;Yoon, Seul Ki;Lee, Nah Hyun;Kang, Kyung Jin
    • Journal of Dairy Science and Biotechnology
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    • v.33 no.2
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    • pp.111-118
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    • 2015
  • Probiotic, prebiotic, and synbiotic substances as well as microorganisms were added to infant formula in an attempt to influence the intestinal microflora with an aim to stimulate the growth of lactic acid bacteria, especially bifidobacteria and lactobacilli. Over the last 10 years, new synbiotic infant formulas containing probiotics and prebiotics have been proposed in order to simulate the effect of breast-feeding on the intestinal microflora. Owing to their synergistic effect, the new synbiotics are expected to be more helpful than using probiotics and prebiotics individually. Maintenance of the viability of the probiotics during food processing and the passage through the gastrointestinal tract should be the most important consideration, since a sufficient number of bacteria ($10^8cfu/g$) should reach the intended location to have a positive effect on the host. Storage conditions and the processing technology used for the manufacture of products such as infant formula adversely affect the viability of the probiotics. When an appropriate and cost-effective microencapsulation methodology using the generally recognized as safe (GRAS) status and substances with high biological value are developed, the quality of infant formulas would improve. The effect of probiotics may be called a double-effect, where one is an immunomodulatory effect, induced by live probiotics that advantageously alter the gastrointestinal microflora, and the other comprises anti-inflammatory responses elicited by dead cells. At present, a new terminology is required to define the dead microorganisms or crude microbial fractions that positively affect health. The term "paraprobiotics" (or ghost probiotics) has been proposed to define dead microbial cells (not damaged or broken) or crude cell extracts (i.e., cell extracts with complex chemical composition) that are beneficial to humans and animals when a sufficient amount is orally or topically administered. The fecal microflora of bottle-fed infants is altered when the milk-based infant formula is supplemented with probiotics or prebiotics. Thus, by increasing the proportion of beneficial bacteria such as bifidobacteria and lactobacilli, prebiotics modify the fecal microbial composition and accordingly regulate the activity of the immune system. Therefore, considerable attention has been focused on the improvement of infant formula quality such that its beneficial effects are comparable to those of human milk, using prebiotics such as inulin and oligosaccharides and potential specific probiotics such as bifidobacteria, which selectively stimulate the proliferation of beneficial bacteria in the microflora and the indigenous intestinal metabolic activity of the microflora.

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Comparison of Antioxidant, Cytotoxicity and Flavonoid Content of Stachys sieboldii Miq. vs. Lycopus lucidus Turcz. Leaf Extracts (초석잠 및 택란 잎 추출물의 항산화 및 세포독성 활성과 총 플라보노이드 함량 비교)

  • Na, Eun;Lee, Jung Woo;Lim, Sun Young
    • Journal of Life Science
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    • v.30 no.2
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    • pp.147-155
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    • 2020
  • In this study, the antioxidant and cytotoxic effects and the flavonoid contents of leaf extracts from Stachys sieboldii Miq. and Lycopus lucidus Turcz. were compared. The flavonoid contents of the acetone + methylene chloride (A+M) and methanol (MeOH) extracts of L. lucidus Turcz. leaves were 55.7 and 233.2 mg/g, respectively. In a DPPH assay, A+M and MeOH extracts from L. lucidus Turcz leaves had a greater scavenging effect than those of S. sieboldii Miq. leaves (p<0.05). In an ABTS assay, MeOH extracts from S. sieboldii Miq. and L. lucidus Turcz (0.5 mg/ml concentration) leaves had scavenging effects of 85% and 91%, respectively (p<0.05), suggesting that both of the MeOH extracts had greater scavenging effects than both A+M extracts. In a 120 min ROS production assay, all tested extracts decreased the cellular ROS production induced by H2O2 compared to that produced by exposure to the extract-free control. The MeOH extract from L. lucidus Turcz leaves had a greater inhibitory effect on cellular ROS production (p<0.05). Treatment with A+M and MeOH extracts from both S. sieboldii Miq. and L. lucidus Turcz. leaves showed a dose-dependent increased cytotoxicity against the growth of AGS, HT-29 cancer cells, and HT-1080 (p<0.05). Both A+M extracts had a greater inhibitory effect on the growth of all cancer cells than both MeOH extracts. These results suggest that the MeOH extract of L. lucidus Turcz. leaves is effective in scavenging free radicals and inhibiting cellular oxidation, while the A+M extract inhibits proliferation of three types of cancer cell.

Screening of Korean Medicinal Herbs for Hormonal Activities using Recombinant Yeast Assay and MCF-7 Human Breast Cancer Cells (재조합효모와 MCF -7 사람유방암세포주를 이용한 한국산 약용식물의 호르몬 활성 스크리닝)

  • Yang Se-Ran;Hong Hee-Do;Cho Sung-Dae;Ahn Nam-Shik;Jung Ji-Won;Park Joon-Suk;Jo Eun-Hye;Hwang Jae-Woong;Sun bo;Park Jung-Ran;Lee Seong-Hun;Jung Ji-Youn;Choi Changsun
    • Journal of Food Hygiene and Safety
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    • v.20 no.1
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    • pp.1-6
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    • 2005
  • To investigate whether there are estrogenic and anti-estrogenic activities in various medicinal herbs and discover prominent chemo-preventive agents, we screened and compared the ethanol extracts of 9 plants through the recombinant yeast assay and MCF-7 human breast cancer cell assay, In recombinant yeast assay, seven medicinal herbs showed estrogenicity, and four extracts showed androgenecity. In MCF-7 proliferation assay, the growth of MCF-7 cells was inhibited by eight extracts before and even after co-treatment with bisphenol A. It is interesting that the extracts of Glycyrrhiza uralensis, Cassia tora, Syringa velutina, Zingiber officinale, Malva verticillata, and Panax ginseng C.A. Meyer exhibited inhibitory effects as phytoestrogens in estrogen-responsive human breast cancer cells. This study suggests that some Korean medicinal herbs might be considered as phytoestrogens and be useful to further analyze those plants which contain the estrogenic effect in order to identify the active principles.

The Role of Phosphofructokinase-2/Fructose-2,6-bisphosphatase 2 (PFKFB2) in Wnt-induced Epithelial-mesenchymal Transition (Wnt에 의한 epithelial-to-mesenchymal transition에서 PFKFB2의 역할)

  • Lee, Su Yeon;Ju, Min Kyung;Jeon, Hyun Min;Kim, Cho Hee;Park, Hye Gyeong;Kang, Ho Sung
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1245-1255
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    • 2017
  • Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.

Chondrogenesis of Human Adipose Tissue Derived Mesenchymal Stem Cells (ATMSCs) Seeded in Gelatin-Chondroitin-Glucosamine Scaffold (Gelatin-Chondroitin-Glucosamine Scaffold에 접종한 인간지방조직-유래 중간엽 줄기세포의 연골형성)

  • Kim, Eung-Bae;Hong, Soon-Gab;Do, Byung-Rok;Kim, Hae-Kwon;Lee, Joon-Yeong
    • Development and Reproduction
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    • v.15 no.2
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    • pp.99-111
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    • 2011
  • The present experiment was performed to evaluate the chondrogenic differentiation potential of human adipose tissue-derived mesenchymal stem cells (ATMSCs) in the chondrogenic induction medium (CIM) with transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and to evaluate the chondrogenic differentiation of ATMSCs seeded in gelatin-chondroitinglucosamine scaffold (GCG-scaffold). ATMSCs and mouse chondrocytes were cultured in the basic medium and CIM without TGF-${\beta}1$ (CIM1) or with TGF-${\beta}1$ (CIM2) for chondrogenic differentiation potential. The chondrogenic differentiation of ATMSCs was evaluated by glycosaminoglycan (GAG) synthesis and histochemical staining. In pellet culture, GAG synthesis of ATMSCs and chondrocyte was increased in culture on 14 days, but higher in CIM1 than basic medium, especially highest in CIM2. Cartilage matrix was observed in ATMSCs cultured in CIM2 on 14 days by Safranin O and trichrome staining. In well plate culture, proliferation of ATMSCs was continuously increased in culture on 10 days and higher in CIM than basic medium. The cell adhesion rate of ATMSCs seeded in flask or scaffolds was continuously increased during culture period, but higher in scaffold than flask. GAG synthesis of ATMSCs seeded in scaffolds showed no change in control group. In the CIM groups, GAG synthesis of ATMSCs was continuously increased than control group during culture period, especially very high in CIM2 and in the GCG-scaffold was slightly higher than the gelatin scaffold (G-scaffold). The present results demonstrated that ATMSCs showed an low chondrogenic differentiation potential, compared to mouse chondrocytes for 14 days of culture. TGF-${\beta}1$ is important factor in chondrogenic differentiation of ATMSCs. Gelatin scaffold was considered to increasing the effective chondrogenic differentiation environment. ATMSCs seeded in GCG-scaffold was more effective in chondrogenesis than in G-scaffold. Conclusively, the present results demonstrated that the treatment of chondroitin and glucosamine in the scaffold was more effective to promote the cartilage matrix formation.

The Signal Transduction Mechanisms on the Intestinal Mucosa of Rat Following Irradiation (방사선조사후 백서소장점막에서 발생하는 신호전달체계에 관한 연구)

  • Yoo Jeong Hyun;Kim Sung Sook;Lee Kyung Ja;Rhee Chung Sik
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.79-95
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    • 1997
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

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Effect of Clonorchis sinensis Excretory-secretory Product on the Cultured SD Rat Bile Duct Fibroblast (배양된 흰쥐 담관 섬유모세포에 대한 간흡충 분비배설 물질의 영향)

  • Kwon, Jung-Nam;Min, Byoung-Hoon;Lee, Haeng-Sook;Kim, Soo-Jin;Joo, Kyoung-Hwan
    • Applied Microscopy
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    • v.39 no.2
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    • pp.117-124
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    • 2009
  • Clonorchis sinensis is the most important widely distributed parasite of the human bile duct in East Asia and the most prevalent parasitic helminth in Korea. The prevalence rate of human clonorchiasis has remained at about 2.9% in Korea. C. sinensis induces dilatation of the duct, hyperplasia of the mucosa, metaplasia or neoplasia of the mucosal epithelium, periductal inflammation and fibrosis, and thickening of the ductal wall. Fibroblast are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may also contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. In this study, ultrastructural changes, the distribution of lectin receptors and actin protein in cultured SD rat bile duct fibroblast after infection of C. sinensis were observed. Experimental group had been divided into four groups: normal bile duct fibroblast cultured in basal media (G1); C. sinensis infected bile duct fibroblast cultured in basal media (G2); normal bile duct fibroblast cultured in basal media containing excretory-secretory product (ESP) (G1-1); C. sinensis infected bile duct fibroblast cultured in basal media containing ESP (G2-1). Overall, once a host is infected by C. sinensis, it affects the host to the extent that sialic acid of ductal fibroblast is increased. Number of cytoplasmic process of SD rat bile duct fibroblast was increased. Actin protein and sialic acid were located in cell surface. Fibroblast induced by C. sinensis was not recovered to normal fibroblast. The cytoplasm bulk and cytoplasmic process were increased whereas the growth rate of the fibroblast of infected SD rat was reduced rather than that of normal fibroblast. In result, it inhibits fibroblast proliferation and increases actin protein on fibroblast cytoplasm, and so causes fibroblast metamorphosis and cellular mutation.