• Title/Summary/Keyword: cell cycle arrest

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Study of the Cytotoxic Protective Effects of Jinsimyusaeng-hwan (Modified Ojayeonjong-hwan) Against Oxidative Stress (산화 스트레스에 대한 진심유생환(오자연종환 가감방) 추출물의 세포 독성 보호 효과에 관한 연구)

  • Yujin Jung;Sanghoon Hong;Myungho Jin
    • Journal of Society of Preventive Korean Medicine
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    • v.28 no.2
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    • pp.113-130
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    • 2024
  • Objectives : This study was conducted to evaluate the cytotoxic protective effects of Jinsimyusaeng-hwan (Modified Ojayeonjong-hwan) against oxidative stress. Methods : 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid)(ABTS) radical scavenging activity and ferric reducing ability of plasma (FRAP) method were used to estimate the antioxidant activity of Jinsimyusaeng-hwan. C2C12 myoblasts were used to reevaluate the antioxidant effects. And apoptosis analysis, mitochondrial membrane potential analysis, measurement of intracellular reactive oxygen species levels were conducted to investigate antioxidant activity of Jinsimyusaeng-hwan. Results : In comparison of DPPH free radical and ABTS cationic radical scavenging activity, it increased as the concentration of water extracts of Jinsimyusaeng-hwan(WEJ) and 70% ethanol extracts of Jinsimyusaeng-hwan (EEJ) increased. In the results of comparing the total phenol content and reducing power using the FRAP method, extracts with high total phenol content also showed high reducing power. In comparison of the protective effect against H2O2-induced oxidative stress in C2C12 myoblasts, WEJ had no significant effect, but the EEJ inhibited H2O2-mediated cytotoxicity in a concentration-dependent manner. The cytotoxic protective effect of EEJ against oxidative stress in C2C12 myoblasts was correlated with their inhibitory effects on H2O2-induced apoptosis and cell cycle arrest. In H2O2-treated C2C12 myoblasts, the apoptosis inhibitory effects of EEJ were associated with suppression of mitochondrial dysfunction and DNA damage. The protective effect of EEJ against H2O2-induced oxidative stress in C2C12 myoblasts were directly related to the inhibition of ROS generation. Conclusion : Jinsimyusaeng-hwan extracts have cytotoxic protective effects against oxidative stress, and it was better in 70% ethanol extract than in water extract.

MicroRNA-23b is a Potential Tumor Suppressor in Diffuse Large B-cell Lymphoma (미만성 거대 B 세포 림프종(DLBCL)에서 microRNA-23b의 잠재적 종양 억제자로서의 효과)

  • Nam, Jehyun;Kim, Eunkyung;Kim, Jinyoung;Jeong, Dawoom;Kim, Donguk;Kwak, Bomi;Kim, Sang-Woo
    • Journal of Life Science
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    • v.27 no.2
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    • pp.149-154
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    • 2017
  • Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3',5' monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5'AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP's effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3' untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b's effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.

Effects of Baicalin on Gene Expression Profiles during Adipogenesis of 3T3-L1 Cells (3T3-L1 세포의 지방세포형성과정에서 Baicalin에 의한 유전자 발현 프로파일 분석)

  • Lee, Hae-Yong;Kang, Ryun-Hwa;Chung, Sang-In;Cho, Soo-Hyun;Yoon, Yoo-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.1
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    • pp.54-63
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    • 2010
  • Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

Attenuation of the Corticosterone-induced Antiproliferative Effect on Human Neuroblastoma SH-SY5Y Cells Using Hot-water Extract from Liriope muscari (Corticosterone에 의해 유도된 인간의 신경모세포종 SH-SY5Y 세포 증식 억제를 완화시키는 맥문동 열수 추출물의 효과에 관한 연구)

  • Lee, Jong Kyu;Kim, Sang-Bo;Seo, Yong Bae;Kim, Gun-Do
    • Journal of Life Science
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    • v.28 no.5
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    • pp.517-523
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    • 2018
  • Elevated levels of cortisol caused by chronic stress may lead to neuron damage in the hippocampus by activating the glucocorticoid receptors (GRs). In cortisol-deficient animals, corticosterone is known to function as a stress hormone. In humans however, corticosterone is considered a precursor of aldosterone and a glucocorticoid with similar properties to cortisol. Recently, many studies have been conducted on the role of cortisol and other synthetic glucocorticoids like dexamethasone in humans, but the exact function of corticosterone is unknown. This study examined the viability of human neuroblastoma SH-SY5Y cells treated with various concentrations of corticosterone for 24 and 48 hr via MTT assay. The MTT-assay results showed that corticosterone had an antiproliferation effect on SH-SY5Y cells at higher concentrations (500 and $1,000{\mu}M$), while in lower concentrations ($100{\mu}M$), it showed no antiproliferation effect. Cytotoxicity analysis of extracts from three medicinal crops (Liriope muscari, Schisandra chinensis, and Wolfiporia extensa) revealed that they all possessed deleterious effects on SH-SY5Y cells depending on dosage. However, it was observed that, at a concentration of $500{\mu}g/ml$, Liriope muscari attenuated the corticosterone-induced antiproliferation on SY-SH5Y cells and restored cell growth after 48 hours of treatment. The study examined the synergistic effect of six mixtures each containing $500{\mu}g/ml$ of Liriope and various concentrations of Schisandra (50 or $100{\mu}g/ml$) and Wolfiporia (10, 30, and $50{\mu}g/ml$). The results showed minor growth-restoration activity but less than that of Liriope muscari only, suggesting that Schisandra and Wolfiporia had no additive or synergistic effects.

Antioxidant activity of Bamboo powder and its immunoreactivity in the pig (대나무 분말의 항산화력과 돼지의 면역 활성에 미치는 영향)

  • Song, Yuno;Chu, Gyo-Moon;Jang, Sun-Hee;Goo, Ae-Jin;Ko, Yeoung-Gyu;Ha, Ji Hee;Lee, Jae-Young;Kang, Suk-Nam;Song, Young-Min;Cho, Jae-Hyeon
    • Korean Journal of Veterinary Service
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    • v.37 no.2
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    • pp.111-122
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    • 2014
  • The present study was designed to explore the antioxidant effect of Bamboo powder and its immunoreactivity in pigs. We investigated the functional properties of Bamboo extracts by means of measuring the contents of total polyphenols and flavonoid as well as determining ABST, DPPH radical scavenging activity, and hydroxyl radical scavenging activity and anticancer activity. The total phenolic compound and flavonoids contents of Bamboo extracts were 171.25 mg/g and 127.5 mg/g, respectively. The DPPH radical, hydroxyl radical, ABST radical scavenging activity of Bamboo extracts were 17.3%, 12.5% and 21.5%, respectively. Evidenced by MTT and cell cycle assay, Bamboo dose-dependently inhibited the cell proliferation and induced G0/G1-phase arrest in CHO cells at concentrations of 100, 250, and 500 ${\mu}g/ml$ Bamboo extracts. More than 80% of apoptotic cells were observed by staining with annexin V in 500 ${\mu}g/ml$ Bamboo-treated CHO cells, indicating that Bamboo had potent anticancer activities. Next, to investigate the effect of Bamboo on cytokine, immunoglobulin concentration, and blood compositions, flatting pigs were fed with Bamboo powder for 38 days. Flatting pigs were divided into 4 groups; basal diet (control), basal diet supplemented with 1% Bamboo powder (T1), 2% Bamboo powder (T2), and 3% Bamboo powder (T3). The level of hemoglobin increased in the all Bamboo-fed groups compared with the normal control group. In particular, platelet levels in the all Bamboo-treated groups increased by approximately 90% compared with the levels from pig on a normal control. Serum levels of immunoglobulins (IgG, IgA) in the pigs fed Bamboo powder were modestly increased, and the interferon-${\gamma}$ level also was strongly increased in 2% or 3% Bamboo-fed groups compared with the levels in control groups. Together, these results demonstrated that Bamboo extracts had an effective capacity of scavenging for ABTS, DPPH, and hydroxyl radicals and showed correlation with potent phenol and flavonoid contents, thus suggesting its antioxidant potential. Moreover, administration of Bamboo in 2~3% improved blood parameters and platelets, and especially immunity-related ones such as IgG, IgA, and interferon-${\gamma}$, leading to be potential feed additives in flatting pigs.

Combined Treatment of Nonsteroidal Anti-inflammatory Drugs and Genistein Synergistically Induces Apoptosis via Induction of NAG-1 in Human Lung Adenocarcinoma A549 Cells (인간 A549 폐암세포에서 비스테로이드성 항염증제와 genistein의 복합처리에 의한 NAG-1 의존적 세포사멸 증진 효과)

  • Kim, Cho-Hee;Kim, Min-Young;Lee, Su-Yeon;Moon, Ji-Young;Han, Song-Iy;Park, Hye-Gyeong;Kang, Ho-Sung
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1073-1080
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    • 2009
  • A number of studies have demonstrated that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risks of colorectal, oesophageal and lung cancers. NSAIDs have been shown to exert their anti-cancer effects through inducing apoptosis in cancer cells. The susceptibility of tumor cells to anti-tumor drug-induced apoptosis appears to depend on the balance between pro-apoptotic and anti-apoptotic programs such as nuclear factor kB (NF-kB), phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) and MEK1/2-ERK1/2 pathways. We examined the effects of pro-survival PI3K and ERK1/2 signal pathways on cell cycle arrest and apoptosis in response to NSAIDs including sulindac sulfide and NS398. We show that simultaneous inhibition of the Akt/PKB and ERK1/2 signal cascades could synergistically enhance the potential pro-apoptotic activities of sulindac sulfide and NS398. Similar enhancement was observed in cells treated with sulindac sulfide or NS398 and 100 ${\mu}$M genistein, an inhibitor of receptor tyrosine kinases (RTKs) that are upstream of PI3K and MEK1/2 signaling. We further demonstrate that NAG-1 is induced and plays a critical role(s) in apoptosis by NSAIDs-based combined treatment. In sum, our results show that combinatorialtreatment of sulindac sulfide or NS398 and genistein results in a highlysynergistic induction of apoptotic cell death to increase the chemopreventive effects of the NSAIDs, sulindac sulfide and NS398.

Clinical Analysis According to $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ Expression in Gastric Cancer (위암에서의 $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ 단백 발현)

  • Kim, Sin-Sun;Park, Yong-Geun;Jun, Kyong-Hwa;Jung, Hun;Song, Gyo-Young;Kim, Jin-Joo;Chin, Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Lim, Keun-Woo;Kim, Seung-Nam;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.6 no.1
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    • pp.36-42
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    • 2006
  • Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

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