• Title/Summary/Keyword: Bcl2-A1

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Induction of Apoptosis Signaling by a Glycoprotein of Capsosiphon fulvescens in AGS Cell (매생이 (Capsosiphon fulvescens) 당단백질에 의한 인간 위암세포 사멸기전)

  • Kim, Young-Min;Kim, In-Hye;Nam, Taek-Jeong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.44 no.3
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    • pp.216-224
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    • 2011
  • Capsosiphon fulvescens is well-known green sea algae that, in recent years, has been proposed as a potential anticancer drug. In this study, we found that C. fulvescens glycoprotein (Cf-GP) had pro-apoptotic effects on human gastric carcinoma cells. By SDS-PAGE, we confirmed that C. fulvescens extract contained a glycoprotein. Using H33342 staining, we found that the Cf-GP caused cell death in a does-dependent manner, while an MTS assay showed decreased cellular viability due to induction of apoptosis. To determine the effect of Cf-GP on apoptosis-related cellular events, cells were treated with Cf-GP and the expression of several apoptosis-related protein was determined by Western blotting. Our results indicate that Cf-GP activated both a caspase cascade and PARP, which is a substrate of caspase-3, caspase-8 and the Bcl-2 family proteins. In addition, we assessed caspase-3, and -8 activation and annexin V staining. Our results revealed a cell cycle arrest, itself leading to an increased percentage of sub-G1 cells. Our findings indicate that Cf-GP may be a source of bio-functional material with therapeutic effects on human gastrointestinal cancer.

The Effects of Yunpyesan on Cell Proloferation, Apoptosis and Cell Cycle Progression of Human Lung Cancer A549 Cells (윤폐산에 의한 폐암세포 증식억제기전에 관한 연구)

  • Kang Yun-Keong;Park Dong Il;Lee Jun Hyuk;Choi Yung Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.4
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    • pp.745-755
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    • 2002
  • To examine the effects of Yunpyesan on the cell proliferation of A549 human lung carcinoma cell line, we performed various experiments such as dose-dependent effect of Yunpyesan on cell proliferation and viability, morphological changes, quantification of apoptotic cell death and alterations of apoptosis/cell cycle-regulatory gene products. Yunpyesan declined cell viability and proliferation in both a dose- and a time-dependent manner. The anti-proliferative effect by Yunpyesan treatment in A459 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Yunpyesan Induced apoptotic cell death in a time-dependent manner, which was associated with degradation of poly-(ADP-ribose) polymerase (PARP), an apoptotic target protein, without alterations of the balance between Bcl-2 and Bax expressions. DNA flow cytometric histograms showed that population of G1 phase of the cell cycle was increased by Yunpyesan treatment in a dose-dependent manner. Western blot analysis revealed that cyclin D1 and A were reduced by Yunpyesan treatment, whereas cyclin dependent kinase (Cdk) inhibitor p27 was markedly increased in a time-dependent fashion. The level of tumor suppressor p53 proteins was also increased by Yunpyesan treatment and its increase might be linked to increase of Cdk inhibitor p27. In addition, Mdm2, negative regulator of p53, was down-regulated by Yunpyesan treatment. Since the expression of retinoblastome protein (pRB), a key regulator of G1/S progression, was reduced by Yunpyesan treatment, we supposed that phosphorylation of pRB might be also blocked. The present results indicated that Yunpyesan-induced inhibition of lung cancer cell proliferation is associated with the induction of apoptosis and the blockage of G1/S progression.

Probiotic Effects of Lactobacillus plantarum and Leuconostoc mesenteroides Isolated from Kimchi (김치에서 분리한 Lactobacillus plantarum과 Leuconostoc mesenteroides의 프로바이오틱 효과)

  • Lee, Kyung-Hee;Bong, Yeon-Ju;Lee, Hyun Ah;Kim, Hee-Young;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.1
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    • pp.12-19
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    • 2016
  • The probiotic effects of kimchi lactic acid bacteria (LAB), Lactobacillus plantarum (Lab. plantarum) and Leuconostoc mesenteroides (Leu. mesenteroides), were studied. Lab. plantarum KCCM 11352P (LPpnu) and Leu. mesenteroides KCCM 11353P (LMpnu) were isolated from kimchi and were the predominant LAB. We compared their probiotic effects with Lactobacillus rhamnosus GG (LRgg), a well-known probiotic LAB. LPpnu showed better probiotic activities than LRgg. LMpnu also exhibited almost equal activities as LRgg. These two kimchi LAB strains exhibited resistance to gastric and bile acid, adhesion to intestines, and thermal stability. In particular, LPpnu showed excellent probiotic properties. In addition, LPpnu showed greater antioxidant activity by scavenging DPPH radicals or hydroxyl radicals than LMpnu or LRgg. LPpnu also inhibited growth of HT-29 human colon cancer cells by inducing apoptosis, increasing Bax and suppressing Bcl-2 expression compared to LMpnu or LRgg. Taken together, LPpnu and LMpnu could be used as probiotics, and LPpnu exhibited the most beneficial probiotic activities with anti-oxidant and anti-cancer properties.

The Anti-cancer Effects of Bigihwan, Daechilgithang, and Mokwhyangbinranghwan Ethanol Extracts in Human Hepatocellular Carcinoma Cells (인체 간암세포에서 비기환(肥氣丸), 대칠기탕(大七氣湯) 및 목향빈랑환(木香檳榔丸)의 항암 활성 비교)

  • Kim, So Young;Hong, Su Hyun;Choi, Sung Hyun;Cheong, JaeHun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.30 no.5
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    • pp.460-467
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    • 2020
  • Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the word. Although radiation and chemotherapy are generally effective, there are various side effects that greatly limit the effectiveness of these treatments. Therefore, traditional herbs may have potential as important resources for the discovery of liver cancer therapeutics. In this study, we selected three Korean herbal medicine formulas from the Donguibogam, namely Bigihwan (BGH), Daechilgithang (DCGT), and Mokwhyangbinranghwan (MHBRH), and evaluated their anti-cancer effects on HCC cells. According to our results of three ethanol extracts, BGH was more effective at suppressing HCC growth than DCGT or MHBRH. Furthermore, flow cytometry analysis showed that inhibition of HCC proliferation by the three extracts was associated with the induction of apoptosis and autophagy. In particular, BGH significantly increased mitochondrial impairment and showed the possibility of inducing mitophagy in comparison with the other two extracts. BGH prominently upregulated the levels of microtubule-associated protein light chain-3 which was accompanied by a decrease in the expression of anti-apoptotic Bcl-2 without altering the expression of pro-apoptotic Bax. In addition, the levels of PTEN-induced kinase 1 were also markedly increased in BGH-treated HCC cells. Moreover, autophagy blocking improved cell viability and reduced apoptosis after the three treatments, indicating that autophagy by these extracts enhances HCC cells against cytotoxicity. In conclusion, our findings show that BGH demonstrates the highest anti-cancer activity among the three formulas and inhibits the proliferation of HCC cells through autophagy induction.

Morphology Evolution of GaAs(100) Surfaces during Inductively Coupled Plasma Etching at Biased Potential (유도결합 플라즈마 식각시 bias에 의한 GaAs(100) 표면의 형태 변화)

  • Lee, Sang-Ho
    • Journal of the Korean Vacuum Society
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    • v.16 no.4
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    • pp.250-261
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    • 2007
  • We present the morphological evolution at different source powers in the ion-enhanced etching of GaAs(100) in $BCl_3-Cl_2$ plasma. With little ion bombardment at floating potential, the surface develops <110> ridges and {111} facets, as it does in purely chemical etching. Higher source power (900 W) produces well developed crystallographic surfaces while lower source power (100 W) produces poorly developed crystallographic surfaces. This is attributed to the availability of excited reactive species (chlorine atoms) depending on source powers. With more concentration of the reactive species at higher source powers, the surface of GaAs(100) would be a surface that is expected from thermodynamics while the surface morphology would be determined by sputtering in the lack of reactive species. Statistical analysis of the surfaces, based on scaling theory, revealed two spatial exponents: one (smaller than one) is formed by atomic scale mechanisms, the other (larger than one) is formed by larger scale mechanisms which is believed to develop facets. When samples are biased, the surfaces experienced bombardment resulting in suppression of ridge formation at high source power and islands formation at low source power.

α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice

  • Chan Lee;Jung-Hee Jang;Gyu Hwan Park
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.411-416
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    • 2023
  • Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

Effects of Fluid Shear Stress on 3T3-L1 Preadipocytes (유체전단응력에 의하여 3T3-L1 지방세포가 받는 영향)

  • Lee, Jeongkun;Lee, Yeong Hun;Jin, Heewon;Lee, Seohyun;Kim, Chi Hyun
    • Journal of Biomedical Engineering Research
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    • v.39 no.4
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    • pp.168-174
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    • 2018
  • Adipocytes affect obesity through the regulation of lipid metabolism. Physical loading is an important regulator of fat tissue. There are ongoing in vitro studies inducing mechanotransduction on 3T3-L1 preadipocytes with mechanical stimulus in order to treat obesity by inhibiting adipogenesis and provoking cell death. In this study, our goal was to suggest a new therapy for obesity by investigating whether fluid shear stress (FSS) changes transcription factors on 3T3-L1 related with adipogenesis and cell death. FSS loading was applied to 3T3-L1 preadipocytes at 1Pa and 1Hz. After loading, bright field images were taken and an immunofluorescence assay was conducted to observe actin stress fiber formation. Western blot analysis was conducted to identify the activation of the ERK pathway as well as the adipogenic factors, which including C/EBPs and $PPAR{\gamma}$. The expression of osteopontin, a protein related to inflammation in adipose tissue, and cell death related factors, Bax, Bcl-2, and Beclin, were also measured. Results showed that FSS stimulated the formation of actin stress fibers in 3T3-L1 and also that the activation of C/EBPs decreased significantly when compared with the control group. $PPAR{\gamma}$ activation in the 2 hour FSS group was lower than the 1 hour FSS group, which implied that the results were time dependent. Additionally, there were no differences in the expression of cell death factors after FSS loading. In summary, similar to other fibroblasts, the formation of actin stress fibers induced by mechanotransduction may affect the differentiation of 3T3-L1, leading to inhibition of adipogenesis and inflammation.

Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer's Disease

  • Xu, Fanxing;He, Bosai;Xiao, Feng;Yan, Tingxu;Bi, Kaishun;Jia, Ying;Wang, Zhenzhong
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.71-77
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    • 2019
  • Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer's disease (AD) induced by $A{\beta}_{1-42}$ and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin ($100{\mu}g/kg/day$), the cognitive impairment of mice induced by $A{\beta}_{1-42}$ was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and $A{\beta}_{1-42}$ accumulation in hippocampus. $A{\beta}_{1-42}$ induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression,suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

The Extract of Pseudomonas aeruginosa Induces the Apoptosis of the Human Colorectal Cancer Cell Line, HCT 116 Cells, via Mitochondrial Pathway

  • Yang, Eun-Ju;Chang, Jeong-Hyun
    • Biomedical Science Letters
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    • v.18 no.1
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    • pp.16-21
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    • 2012
  • Although there are many potential cytotoxic molecules released from bacteria, the role of these molecules on the apoptosis of various cancer cells is not well understood. Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative, aerobic and rod-shaped bacterium, and has a number of virulence factors. To understand the cytotoxic effect of bacterial extracts on the colorectal cancer cell line, HCT 116 cells, we examined alteration of the cell viability, proliferation, cell cycle and apoptosis of HCT 116 cells after treatment with extract of P. aeruginosa (PaE). These cytotoxicity of PaE occurred in a time- and a dose-dependent manners. In addition, PaE arrested the cell cycle of HCT 116 cell in a time-dependent manner. PaE inhibited the protein levels of Bcl-2 and induced the release of cytochrome c from mitochondria of HCT 116 cells. The decrease of procaspase-3 was induced by the treatment of PaE. These results indicate that PaE has a cytotoxicity in HCT 116 cells via the induction of apoptosis associated with mitochondrial pathway. Therefore, PaE may used as the potential target for the treatment of colorectal cancer.

Methanol Extracts of Codium fragile Induces Apoptosis through G1/S Cell Cycle Arrest in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Lee, Seul Ah;Park, Bo-Ram;Moon, Sung Min;Kim, Do Kyung;Kim, Chun Sung
    • International Journal of Oral Biology
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    • v.43 no.2
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    • pp.61-68
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    • 2018
  • Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.