• 제목/요약/키워드: growth inhibitory effects

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Protective Effects on Gastric Lesion of Ursolic acid (Ursolic acid의 위 손상에 대한 방어 효과)

  • Kim, Sun Whoe;Hwang, In Young;Lee, Sun Yi;Jeong, Choon Sik
    • Journal of Food Hygiene and Safety
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    • v.31 no.4
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    • pp.286-293
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    • 2016
  • This study is an experiment for gastric protective effects of ursolic acid. In order to identify the effects of ursolic acid on gastrointestinal disorder, acute and chronic gastritis were also observed using HCl ethanol and indomethacin-induced gastric lesion models, respectively. As for gastric acid, it was also identified through proton pump ($H^+/K^+-ATPase$) inhibiting activity. In regards to protective factor for gastric damage, prostaglandin $E_2$ ($PGE_2$) was quantitatively analyzed. Antibacterial activity experiment was done on Helicobacter pylori (H.pylori), which is known to be the causing factor of chronic gastritis, gastric ulcer and gastric cancer. By making use of AGS cell, it was confirmed that ursolic acid was involved in apoptosis of gastric cancer cell through 4',6-diamidino-2-phenylindol (DAPI) staining and flow cytometry analysis. As a result, ursolic acid reduced gastric lesions caused by HCl ethanol and indomethacin. Ursolic acid inhibited acid secretion by inhibiting proton pump ($H^+/K^+-ATPase$), which is the gastric acid secreting enzyme involved at the final phase of gastric acid secretion. And ursolic acid was identified with gastric mucosa protection effects by increasing the concentration of $PGE_2$, a protective factor of gastric mucosa preservation. The antibacterial activity on H. pylori, which is aggressive factor in gastrointestinal disorder, ursolic acid showed inhibitory effects on H. pylori colonization. In the DAPI nuclear staining, unlike the control group, shape of the nucleus has deformed, and has been observed either shrinked cell or chromatin condensation phenomenon. In the Flow cytometry assay, confirmed the growth rate of apoptosis in a concentration-dependent manner.

The Antimicrobial and Growth Inhibitory Effects of Gelidium amansii L. Fractions on Cancer Cell Lines (우뭇가사리 분획물의 항균 및 암세포 성장억제효과)

  • Shin, Hye-Jung;Gang, Dae-Yeon;Shin, Mi-Ok;Bae, Song-Ja
    • Journal of Marine Bioscience and Biotechnology
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    • v.2 no.2
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    • pp.113-119
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    • 2007
  • In this study, we investigated antimicrobial and cytotoxicity effects of Gelidium amansii L., which using methanol, dichloromethane and ethanol were extracted and fractionated into four different types : methanol (GAMM), hexane (GAMH), butanol (GAME) and aqueous (GAMA). The antimicrobial activity was increased in proportion to its concentration by the paper disc method. Among the solvent fractions, The methanol partition layer (GAMM) showed the strongest antimicrobial activities and cytotoxic effects on all cancer cell lines. We also observed quinone reductase (QR) induced effects in all fraction layers of GA on HepG2 cells. The QR induced effects of GAMM on HepG2 cells at $40{\mu}g/mL$ concentration indicated 2.5 with a control value of 1.0.

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Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

  • Shin, Hanna;Eo, Hyeyoon;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.33-41
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    • 2016
  • BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ${\leq}$ FBG ${\leq}$ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on $NF{\kappa}B$ associated inflammatory response (phosphorylated inhibitory kappa B-${\alpha}$, interleukin-$1{\beta}$, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor ${\beta}$-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

Rg3-enriched red ginseng extracts enhance apoptosis in CoCl2-stimulated breast cancer cells by suppressing autophagy

  • Yun-Jeong Jeong;Mi-Hee Yu;Yuna Cho;Min-Young Jo;Kwon-Ho Song;Yung Hyun Choi;Taeg Kyu Kwon;Jong-Young Kwak;Young-Chae Chang
    • Journal of Ginseng Research
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    • v.48 no.1
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    • pp.31-39
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    • 2024
  • Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.

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.

The Effects of Crinum asiaticum on the Apoptosis Induction and the Reversal of Multidrug Resistance in HL-60/MX2

  • Hyun, Jae-Hee; Kang, Jung-Il;Kim, Sang-Cheol;Kim, Elvira;Kang, Ji-Hoon;Kwon, Jung-Mi;Park, Doek-Bae;Lee, Young-Jae;Yoo, Eun-Sook;Kang, Hee-Kyoung
    • Toxicological Research
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    • v.24 no.1
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    • pp.29-36
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    • 2008
  • The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform ($CHCl_3$) fraction and butanol (BuOH) fraction of C. asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the $CHCl_3$ and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced BcI-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The $CHCl_3$ fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the $CHCl_3$ fraction of C. asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C. asiaticum might have a therapeutic potential for the treatment of MDR leukemia.

Investigation of Biological Activities of Enzymatic Hydrolysate of Spirulina (스피루리나 효소가수분해물의 생리활성 탐색)

  • Son, Min-Hee;Park, Keun-Hyoung;Choi, A-Reum;Yoo, Gui-Jae;In, Man-Jin;Kim, Dong-Ho;Chae, Hee-Jeong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.2
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    • pp.136-141
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    • 2009
  • Biological activities of enzymatic hydrolysate of spirulina (EHS) were investigated. EHS showed no significant effects on the growth-stimulating activity for lactic-acid bacteria and antioxidant activity. EHS showed slight in vitro growth-inhibitory effects (15% at 1.42 mg/L) on a human cervical cancer cell line (HeLa). In addition, the anticoagulant activities of EHS were measured based on three different pathways: common, intrinsic and extrinsic pathways. As an indication of anticoagulant activity on common pathway, thrombin time (TT) of EHS (100 mg/L) was measured as 155.6 sec. Activated partial thromboplastin time (aPTT) for intrinsic pathway of EHS (1,000 mg/L) was measured as 95.8 sec. Prothrombin time (PT) based on extrinsic pathway of EHS (1,000 mg/L) was measured as 10.6 sec. These data showed that EHS have influences on anticoagulant factors of common pathway and intrinsic pathway. Consequently it was found that EHS could be used as a functional food for blood circulation.

The Ethanol Extract of Red Ginseng Enhances Anti-Tumor Effects Using Co60 Gamma Irradiation (홍삼의 에탄올 추출물의 감마선 조사를 통한 항암효과 증대)

  • Hur, Jung-Mu;Kim, Dong-Ho
    • Journal of Applied Biological Chemistry
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    • v.54 no.1
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    • pp.15-20
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    • 2011
  • Red ginseng is one of the most popular traditional medicines in Korea. In this study, we developed a new technique in which ethanol extract of $\underline{r}$ed $\underline{g}$inseng (HRG) was exposed to the $Co^{60}$ gamma radiation ranging from 1~5 kGy. The irradiated HRG (IHRG) were analyzed by high performance liquid chromatography (HPLC) to determine any compositional changes of ginsenosides due to irradiation. No appreciable difference was observed in the HPLC pattern of ginsenosides of HRG. Using MTT assay, the cytotoxicity effect was significantly increased by IHRG compared to HRG. The $LD_{50}$ concentration was $30{\mu}g/mL$ for IHRG-1 (1 kGy), and $15{\mu}g/mL$ for IHRG-5 (5 kGy). The evidences of apoptosis, such as nuclei cleavage and Annexin V staining, were observed in the human prostate cancer PC-3 cells treated with the IHRG. Additionally, the level of reactive oxygen species (ROS) was apparently elevated by IHRG. We also studied the inhibitory effect of IHRG on the growth rate of tumor xenografts in BALB/c male mice. The tumor growth rates were inhibited by 56.9 and 76.1% in mice treated with 10 mg/kg of IHRG-1 and IHRG-5, respectively, compared with control group (21.1%). These results suggest that some biologically active and soluble components in HRG can be more effectively enhancement of anti-tumor effects using irradiation.

Modulation of Pituitary Somatostatin Receptor Subtype (sst1-5) mRNA Levels by Growth Hormone (GH)-Releasing Hormone in Purified Somatotropes

  • Park, Seung-Joon;Park, Hee-Soon;Lee, Mi-Na;Sohn, Sook-Jin;Kim, Eun-Hee;Jung, Jee-Chang;Frohman, Lawrence A.;Kineman, Rhonda D.
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.2
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    • pp.79-84
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    • 2003
  • We have previously reported that expression of the somatostatin receptor subtypes, sst1-5, is differentially regulated by growth hormone (GH)-releasing hormone (GHRH) and forskolin (FSK), in vitro. GHRH binds to membrane receptors selectively located on pituitary somatotropes, activates adenylyl cyclase (AC) and increases sst1 and sst2 and decreases sst5 mRNA levels, without significantly altering the expression of sst3 and sst4. In contrast FSK directly activates AC in all pituitary cell types and increases sst1 and sst2 mRNA levels and decreases sst3, sst4 and sst5 expression. Two explanations could account for these differential effects: 1) GHRH inhibits sst3 and sst4 expression in somatotropes, but this inhibitory effect is masked by expression of these receptors in unresponsive pituitary cell types, and 2) FSK inhibits sst3 and sst4 expression levels in pituitary cell types other than somatotropes. To differentiate between these two possibilities, somatotropes were sequentially labeled with monkey anti-rat GH antiserum, biotinylated goat anti-human IgG, and streptavidin-PE and subsequently purified by fluorescent-activated cell sorting (FACS). The resultant cell population consisted of 95% somatotropes, as determined by GH immunohistochemistry using a primary GH antiserum different from that used for FACS sorting. Purified somatotropes were cultured for 3 days and treated for 4 h with vehicle, GHRH (10 nM) or FSK ($10{\mu}M$). Total RNA was isolated by column extraction and specific receptor mRNA levels were determined by semi-quantitative multiplex RT-PCR. Under basal conditions, the relative expression levels of the various somatostatin receptor subtypes were sst2>sst5>sst3=sst1> sst4. GHRH treatment increased sst1 and sst2 mRNA levels and decreased sst3, sst4 and sst5 mRNA levels in purified somatotropes, comparable to the effects of FSK on purified somatotropes and mixed pituitary cell cultures. Taken together, these results demonstrate that GHRH acutely modulates the expression of all somatostatin receptor subtypes within GH-producing cells and its actions are likely mediated by activation of AC.

The Mechanism of Antimutagenic Effect of Cinnamaldehyde on Chemical Mutagenesis (화학적 변이에 대한 Cinnamaldehyde의 항돌연변이)

  • 송근섭;한상배;최동성
    • The Korean Journal of Food And Nutrition
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    • v.10 no.3
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    • pp.407-413
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    • 1997
  • The antimutagenic mechanism of cinnamaldeyde on mutagenesis induced by 4-nitroquinoline-1-oxide(4-NQO) and N-metyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in various DNA repair-deficient strains, E. coli B/r and K-12 series. Cinnamaldehyde did not show any effects not only on the $\beta$-galactosidase activities of GW1060 and GW1103(recA441) which synthesizes $\beta$-galactosidase consitutively at 41$^{\circ}C$ but also on that of GW1107[lexA51 (Def)] in which the SOS response always occur. These results suggest that cinnamaldehyde dose not change the function of RecA which positively controls the SOS response as well as not acting as the repressor like LexA. In addition, no inhibitory effect of cinnamaldehyde was observed on the growth of Trp+ revertant and the delay of viable cell growth was also not found by adding cinnamaldehyde. Despite the decrease in the number of revertants, a significant increase in survival of 4-NQO treated cells was observed in E. coli WP2s(uvrA), ZA159($\Delta$uvrB) and TK603(uvrA). But these effects disappeared in excision-proficient strain WP2(uvrA+) and lexA-deficient strains(CM561 and CM611). The enhancement of survival was not found in WP67(uvrA polA) deficient in polymerase I which ligates the gap between complementary DNA. From the above results, we assume that cinnamaldehyde might show antimutagenic effect by enhancing an error-free recombinational repair system.

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