• Title/Summary/Keyword: 세포생존

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Anti-tumor effect of new compound, 127, through the induction of apoptosis (새로운 화합물 c-127의 세포고사 유도에 의한 항암효과)

  • Baek, Ki Hwan;Han, A Lum;Shin, Sae Ron;Jin, Chun Mae;Yoon, Young Wook;Yu, Seung Taek;Kim, Jong Duk;Choi, Du Young
    • Clinical and Experimental Pediatrics
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    • v.52 no.6
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    • pp.696-700
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    • 2009
  • Purpose : We screened more than 350 compounds with an endoperoxide ring structure in search of an anti-leukemic drug and found that compound 127 (c-127) could induce significant cytotoxicity in HL-60 cells. In this study, we investigated the molecular mechanisms of compound 127-induced antitumor activity on HL-60 cells. Methods : HL-60 cells were cultured in Rosewell Park Memorial Institute 1640 and cell viability was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], a tetrazole assay. Apoptosis was assessed by a DNA fragmentation test. Apoptotic machineries were determined by Western blot analysis. Results : C-127 could induce a cytotoxic effect at 24 h and apoptosis at 6 h, which was demonstrated with MTT assay and DNA fragmentation test, respectively. The apoptotic effect of this drug was caused by the activation of the intracellular caspase-8,3 activation, the cleavage of pro-apoptotic Bid, and the increase of c-Jun expression accompanied with JNK (Jun N-terminal kinases) phosphorylation. On the contrary, it increased the expression of anti-apoptotic Bcl-2 levels, leading to the induction of the induction of anti-apoptotic effect. Taken together, the present study demonstrated that c-127 was a potent inducer of cytotoxicity on HL-60 cells through apoptotic mechanisms, which included the activation of caspase family, the regulation of Bcl-2 family, and the activation of JNK signaling pathway. Conclusion : Our results suggest that c-127 has a strong antitumor activity through the regulation of various apoptotic machineries on HL-60 cells. The compound may be utilized as an effective and potentially therapeutic drug in leukemia.

The Effects of Paeonia Lactiflora Pallas on Inhibition of Oxygen Free Radical, Anti-inflammation and MMP-1 Inhibitory Activity (적작약 꽃 추출물의 활성산소 억제와 항염증 및 MMP-1 발현 억제능 효과에 관한 연구)

  • Leea, Jae-Nam;Kim, Young-Sam
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.3
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    • pp.797-806
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    • 2018
  • This study attempted to investigate the effects of Paeonia Lactiflora Pallas (P. lactiflora) on the inhibition of oxygen free radical, anti-inflammation and MMP-1 inhibitory activity and examine its possibility as a functional cosmetic material. For test methods, the inhibition of oxygen free radical after measuring reactive oxygen species (ROS) in the cell, cytotoxicity assessment and anti-inflammation were measured, and MMP-1 inhibitory effects in the HDF cell were measured. According to the test, the inhibition of ROS was confirmed in RAW 264.7 and HDF cells. In terms of cytotoxicity assessment, 90% or higher cell viability was detected at $5/10{\mu}g/mL$ Paeonia Lactiflora Pallas extract while it was 80% or higher at other concentration levels in both RAW 264.7 and HDF cells. In addition, NO production was inhibited in the RAW 264.7 cell while MMP-1 was significantly inhibited in the HDF cell. The above results reveal a possibility of Paeonia Lactiflora Pallas extract as a functional cosmetic material after confirming the inhibition of ROS synthesis in the cell, antioxidant and anti-inflammatory effects by inhibiting NO synthesis, low toxicity on skin cells and anti-aging effect through MMP-1 inhibition.

Repression of Cathepsin D Expression in Adipocytes by MicroRNA-145 (지방세포에서 microRNA-145에 의한 Cathepsin D의 발현 제어)

  • Kim, Hyun-Ji;Bae, In-Seon;Seo, Kang-Seok;Kim, Sang Hoon
    • Journal of Life Science
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    • v.24 no.7
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    • pp.798-803
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    • 2014
  • Cathepsin D (CtsD), an aspartyl peptidase, is involved in apoptosis, resulting in the release of cytochrome C from mitochondria in cells. Here, we investigated microRNA regulation of CtsD expression in 3T3-L1 cells First, we observed the expression of CtsD in cells in response to doxorubicin (Dox). As expected, the level of CtsD mRNA was increased in 3T3-L1 cells exposed to Dox in a dose-dependent manner. Cellular viability of ectopically expressed CtsD cells was also decreased. Next, we used the miRanda program to search for particular microRNA targeting CtsD. MiR-145 was selected as a putative controller for CtsD because miR-145 had a high mirSVR score. In a reporter assay, the luciferase activity of cells containing the CtsD 3'-UTR region was decreased in cells transfected with miR-145 mimic compared to that of a control. The level of CtsD expression was down-regulated in preadipocytes ectopically expressing miR-145 and up-regulated by an miR-145 inhibitor. Cells also suppressed miR-145 expression when exposed to Dox. The miR-145 inhibitor reduced the cellular viability of 3T3-L1 cells. Taken together, these data suggest that miR-145 regulates CtsD-mediated cell death in adipocytes. These findings may have valuable implications concerning the molecular mechanism of CtsD-mediated cell death in obesity, suggesting that CtaD could be a useful therapeutic tool for the prevention and treatment of obesity by regulating fat cell numbers.

Effect of Ursolic Acid on the Development of Mouse Embryonic Stem Cells under Hypoxia (저산소 상태에서 우르솔산이 배아줄기세포 성장에 미치는 효과)

  • Han, Gi Yeon;Park, Jae Hong;Oh, Keon Bong;Lee, Sei-Jung
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1223-1229
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    • 2013
  • Ursolic acid (UA) a bio-active ingredient found in a variety of fruits and vegetables, and it has potent antioxidant activity. However, the role of UA in mouse embryonic stem (ES) cells is poorly understood. This study investigated the functional role of UA in regulating the development of mouse ES cells under hypoxia. Hypoxia did not exert a significant effect on the undifferentiated state of mouse ES cells. However, it induced reactive oxygen species (ROS) generation and increased the level of lactate dehydrogenase (LDH) production at 48 h of hypoxic exposure. Conversely, oxidative stress induced by hypoxia was significantly inhibited by UA ($30{\mu}M$) pretreatment. Hypoxia significantly decreased cell survival and the level of [$^3H$] thymidine incorporation, both of which recovered following pretreatment of UA. In addition, UA decreased the apoptotic effect of hypoxia by attenuating caspase-3 cleavage or by recovering cellular inhibition of the apoptotic protein (cIAP)-2 and Bcl-2 expression. We further found that UA decreased senescence-associated beta-galactosidase activity. We suggest that UA is a natural antioxidant and one of the functional modulators of hypoxia-induced survival, apoptosis, proliferation, and aging in mouse ES cells.

Influence of Prognostic Factors on Survival Rate of Medulloblastoma Patient with Chemotherapy (항암치료를 받은 수모세포종환아에서 예후인자들이 생존률에 미치는 영향)

  • Shin, Kyung Mi;Choi, Sung Yeon;Won, Sung Chul;Yang, Chang Hyun;Lyu, Chuhl Joo;Suh, Chang Ok;Choi, Joong Uhn;Kim, Byung Soo
    • Clinical and Experimental Pediatrics
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    • v.46 no.2
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    • pp.178-182
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    • 2003
  • Purpose : Brain tumors are the second most common tumor in childhood, and medulloblastomas comprise 15-25% of brain tumors. The well known prognostic factors are age at diagnosis, stage of disease, and extent of surgical excision. In this study, we analysed the prognostic factors in patients who received chemotherapy after excision. Methods : We reviewed the medical records of 61 patients who received chemotherapy among the 94 patients who were diagnosed and treated between Jan 1985 and Sep 2001 in the Department of Pediatrics and Neurosurgery at Severance Hospital. Results : Among the total survival rate of patients who underwent chemotherapy, the 3-yr progression-free survival rate was $66.5{\pm}6.3%$ and the 15-yr progression-free survival rate was $60.3{\pm}6.7%$. The progression-free survival rate for patients with age at diagnosis over 3 yrs old and under 3 yrs old, was $64.5{\pm}7.7%$ and $48.2{\pm}12.9%$ respectively and there was no statistically significant difference. The survival rate of the high vs low risk group by staging was $72.7{\pm}10.5%$ and $54.6{\pm}8.3%$ respectively, and there was no significant difference. The survival rate of patients with total removal vs subtotal removal was $65.8{\pm}11.8%$ and $56.8{\pm}8.2%$ respectively, showing no statistical difference. Conclusion : The reason there is no difference in survival rate according to the traditional prognostic factors is that chemotherapy has improved not only the total survival rate but also the survival rate in patients with poor traditional prognostic factors. So, sufficient removal of tumor followed by proper chemotherapy and radiotherapy is an important factor which influences the survival rate of medulloblastoma patients.

Outcome and risk factors of pediatric hemato-oncology patients admitted in pediatric intensive care unit (소아 중환자실에 입실한 소아 종양/혈액 질환 환자의 예후 및 위험인자)

  • Kim, Bo Eun;Ha, Eun Ju;Bae, Keun Wook;Kim, Seon Guk;Im, Ho Joon;Seo, Jong Jin;Park, Seong Jong
    • Clinical and Experimental Pediatrics
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    • v.52 no.10
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    • pp.1153-1160
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    • 2009
  • Purpose:To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). Methods:We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. Results:Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was $7.0{\pm}5.7$ years and mean duration of PICU stay was $18.1{\pm}22.2$ days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). Conclusion:The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome.

Physiological Properties of Lactobacillus acidophilus 30SC Exposed to Heat Shock Stress (Heat Shock Stress에 의한 Lactobacillus acidophilus 30SC의 생리적 특성)

  • Moon, Yong-Il;Han, Soo-Min;Park, Dong-Jun;Chi, Youn-Tae;Kim, Kwang-Hyun;Oh, Sejong
    • Food Science of Animal Resources
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    • v.25 no.3
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    • pp.350-356
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    • 2005
  • We examined the enhancement of thermotolerance for storage conferred on Lactobacillus acidophilus 30SC by adaptation to different stresses. The viable cells of Lactobacillus acidophilus 30SC were compared with their viability prior to heating at $45,\;55^{\circ}C\;and\;60^{\circ}C$. Heat-adapted ($45^{\circ}C$ for 15 min) L. acidophilus 30SC in MRS broth exhibited higher survivability at lethal temperature of $55^{\circ}C$ than control. Cellular protein profiles of L. acidophilus 30SC during heat adaptation were examined with SDS-PAGE, and scanning electron microscopy. When L. acidophilus 30SC was heat-adapted at $55^{\circ}C$ for 15min, 5 new protein spots of ca $8\~45\;kDa$ size were observed on 2D SDS-PAGE. It was presumed that new proteins of L. acidophilus 30SC were produced to adapt to the environment of higher growth temperature.

Betulinic Acid Induces Apoptosis in Humam Mucoepidermoid Carcinoma Cells Through Regulating Specificity Protein 1 and Its Downstream Molecule, Survivin

  • Lee, Jung-Eun;Jung, Ji-Youn;Yoo, Hyun-Ju;Cho, Sung-Dae
    • Journal of Food Hygiene and Safety
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    • v.28 no.3
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    • pp.202-206
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    • 2013
  • High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

Cytotoxic Activity of Vietnamese Herbal Medicines against A549 Cells (A549세포에 대한 베트남 약용식물의 세포독성)

  • Cuong, Nguyen Manh;Nam, Nguyen-Hai;Kim, Yong;You, Young-Jae;Bae, Ki-Hwan;Sung, Tran Van;Ahn, Byung-Zun
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.64-68
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    • 2002
  • Eighty methanol extracts prepared from Vietnamese plants were tested for their cytotoxic activity against A549 cells, a human lung carcinoma cell line. Nine extracts showed survival rates of tumor cells of less than 30% at $100\:{\mu}g/mL$ of the methanol extracts. Among them, three were less than 15%; Meliosma pinnata (VK03, 4%), Goniothalamus vietnamensis (VK05, 06, 0%), Garcinia sp. (VK50, 51, 0%) and Aglaia aphanamixis (VK63, 11%). Both leaf and root extracts of Goniothalamus vietnamensis and the leaf extract of a Garcinia species completely inhibited the growth of A549 cells at the concentration of $100\:{\mu}g/mL$ methanol extract.

Antioxidant Activity of Mulberry Leaves Extract Fermented by Hericium erinaceum (버섯균사체 발효 뽕잎 추출물의 항산화 활성)

  • Kang, Jung Hoon
    • Journal of the Korean Applied Science and Technology
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    • v.34 no.4
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    • pp.1025-1035
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    • 2017
  • In this study, the hot water extract from Mulberry (Morus alba) Leaves fermented with Hericium erinaceum mycelium (MA-HE) was assessed for antioxidant activity. Radical scavenging activity of MA-HE evaluated using 2,2-diphenyl-1-picrylhydrazyl(DPPH) radical and 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid)(ABTS) radical. MA-HE showed 63% DPPH radical scavenging activity at $500{\mu}g/mL$ and 98.27% ABTS radical scavenging activity at $250{\mu}g/mL$. MA-HE was shown to significantly inhibited DNA strand breakage induced by free radical. MA-HE also inhibited free radical-mediated human serum albumin modification. MA-HE effectively inhibited $H_2O_2$ induced cell death and significantly increased of the 8% cell survival at $100{\mu}g/mL$. MA-HE decreased intracellular reactive oxygen species (ROS) levels in $H_2O_2$-treated cells. The results suggested that MA-HE can contribute to antioxidant and protected cells from oxidative stress-induced cell injury.