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      Induction of Apoptosis Scutellaria baicalensis Georgi Root Extract by Inactivation of the Phosphatidyl Inositol 3-kinase/Akt Signaling Pathway in Human Leukemia U937 Cells

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      https://www.riss.kr/link?id=A106107590

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      다국어 초록 (Multilingual Abstract)

      Background: The roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used in traditional medicine for treatment of various diseases. In this study, we investigated the effects of ethanol extracts of S. baicalensis roots (EESB) on the gr...

      Background: The roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used in traditional medicine for treatment of various diseases. In this study, we investigated the effects of ethanol extracts of S. baicalensis roots (EESB) on the growth ofn human leukemia U937 cells.
      Methods: The effect of EESB on cell viability was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay.
      Apoptosis was determined using 4,6-diamidino-2-phenyllindile staining and flow cytometry. The effects of EESB on the expression of regulatory proteins of apoptosis and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling were determined by Western blotting. Caspase activity and mitochondrial membrane potential (MMP) were measured using flow cytometric analysis.
      Results: EESB significantly inhibited the growth of U937 cells and induced apoptosis, which was associated with down-regulation of anti-apoptotic Bcl-2, up-regulation of pro-apoptotic Bax, the loss of MMP and activation of caspase-9 and -3. We also found that EESB enhanced the expression of death receptors (DRs) and their associated ligands and induced the activation of caspase-8 and truncation of Bid. In addition, EESB suppressed PI3K/Akt signaling and EESB-induced apoptosis and growth inhibition were further increased by inhibition of PI3K activity.
      Conclusions: Our results indicated that the pro-apoptotic effect of EESB was mediated through the activation of DR-mediated intrinsic and mitochondria-mediated extrinsic apoptosis pathways and inhibition of the PI3K/Akt signaling in U937 cells.
      (J Cancer Prev 2019;24:11-19)

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      참고문헌 (Reference)

      1 Adams JM, "Ways of dying: multiple pathways to apoptosis" 17 : 2481-2495, 2003

      2 Wang C, "The role of mitochondria in apoptosis" 43 : 95-118, 2009

      3 Keating J, "Targeting the inhibitor of apoptosis proteins as a novel therapeutic strategy in medulloblastoma" 11 : 2654-2663, 2012

      4 Hensley P, "Targeting caspases in cancer therapeutics" 394 : 831-843, 2013

      5 Watson RW, "Targeting apoptosis in prostate cancer:focus on caspases and inhibitors of apoptosis proteins" 96 (96): S30-S34, 2005

      6 Schneider-Jakob S, "Synergistic induction of cell death in liver tumor cells by TRAIL and chemotherapeutic drugs via the BH3-only proteins Bim and Bid" 1 : e86-, 2010

      7 도미향, "Survivin protects fused cancer cells from cell death" 생화학분자생물학회 50 (50): 361-366, 2017

      8 Li SS, "Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically" 97 : 762-770, 2011

      9 Goc A, "Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis" 12 : 409-, 2012

      10 Park JR, "Scutellaria baicalensis Georgi induces caspase-dependent apoptosis via mitogen activated protein kinase activation and the generation of reactive oxygen species signaling pathways in MCF-7 breast cancer cells" 16 : 2302-2308, 2017

      1 Adams JM, "Ways of dying: multiple pathways to apoptosis" 17 : 2481-2495, 2003

      2 Wang C, "The role of mitochondria in apoptosis" 43 : 95-118, 2009

      3 Keating J, "Targeting the inhibitor of apoptosis proteins as a novel therapeutic strategy in medulloblastoma" 11 : 2654-2663, 2012

      4 Hensley P, "Targeting caspases in cancer therapeutics" 394 : 831-843, 2013

      5 Watson RW, "Targeting apoptosis in prostate cancer:focus on caspases and inhibitors of apoptosis proteins" 96 (96): S30-S34, 2005

      6 Schneider-Jakob S, "Synergistic induction of cell death in liver tumor cells by TRAIL and chemotherapeutic drugs via the BH3-only proteins Bim and Bid" 1 : e86-, 2010

      7 도미향, "Survivin protects fused cancer cells from cell death" 생화학분자생물학회 50 (50): 361-366, 2017

      8 Li SS, "Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically" 97 : 762-770, 2011

      9 Goc A, "Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis" 12 : 409-, 2012

      10 Park JR, "Scutellaria baicalensis Georgi induces caspase-dependent apoptosis via mitogen activated protein kinase activation and the generation of reactive oxygen species signaling pathways in MCF-7 breast cancer cells" 16 : 2302-2308, 2017

      11 Yoon JJ, "Protective effects of Scutellaria baicalensis Georgi against hydrogen peroxide-induced DNA damage and apoptosis in HaCaT human skin keratinocytes" 16 : 426-438, 2017

      12 Assunção Guimarães C, "Programmed cell deaths. Apoptosis and alternative deathstyles" 271 : 1638-1650, 2004

      13 Yang L, "Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide" 63 : 831-837, 2003

      14 Bodur C, "Pramanicin analog induces apoptosis in human colon cancer cells: critical roles for Bcl-2, Bim, and p38 MAPK signaling" 8 : e56369-, 2013

      15 Gao N, "Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways" 2 : e140-, 2011

      16 현승연, "Peroxisome Proliferator-Activated Receptor-Gamma Agonist 4-O-Methylhonokiol Induces Apoptosis by Triggering the Intrinsic Apoptosis Pathway and Inhibiting the PI3K/Akt Survival Pathway in SiHa Human Cervical Cancer Cells" 한국미생물·생명공학회 25 (25): 334-342, 2015

      17 Yuan K, "PARP-1 regulates resistance of pancreatic cancer to TRAIL therapy" 19 : 4750-4759, 2013

      18 Pan TL, "Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway" 139 : 829-837, 2012

      19 Khaw-on P, "Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic MOLT-4 cell line by terpinen-4-ol" 13 : 3073-3076, 2012

      20 Hong GE, "Flavonoids identified from Korean Scutellaria baicalensis Georgi inhibit inflammatory signaling by suppressing activation of NF-κB and MAPK in RAW 264.7 cells" 2013 : 912031-, 2013

      21 Jeong K, "Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice" 18 : 14-, 2011

      22 Liu F, "Effects of poly (ADP-ribose) polymerase-1 (PARP-1) inhibition on sulfur mustard-induced cutaneous injuries in vitro and in vivo" 4 : e1890-, 2016

      23 Hsieh MJ, "Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines" 87 : 1927-1937, 2013

      24 Kresty LA, "Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation" 6 : 33438-33455, 2015

      25 Kalimuthu S, "Cell survival and apoptosis signaling as therapeutic target for cancer: marine bioactive compounds" 14 : 2334-2354, 2013

      26 Fiandalo MV, "Caspase control: protagonists of cancer cell apoptosis" 34 : 165-175, 2012

      27 Farkona S, "Cancer immunotherapy:the beginning of the end of cancer?" 14 : 73-, 2016

      28 Chen J, "Calycosin suppresses breast cancer cell growth via ERβ-dependent regulation of IGF-1R, p38 MAPK and PI3K/Akt pathways" 9 : e91245-, 2014

      29 Ward TH, "Biomarkers of apoptosis" 99 : 841-846, 2008

      30 Chen Xu, "Bioconversion of Flavones During Fermentation in Milk Containing Scutellaria baicalensis Extract by Lactobacillus brevis" 한국미생물·생명공학회 23 (23): 1422-1427, 2013

      31 Zhou Y, "Bioactive and UV protective silk materials containing baicalin - the multifunctional plant extract from Scutellaria baicalensis Georgi" 67 : 336-344, 2016

      32 Miura M, "Apoptotic and nonapoptotic caspase functions in animal development" 4 : a008664-, 2012

      33 Reed JC, "Apoptosis-targeted therapies for cancer" 3 : 17-22, 2003

      34 Wong RS, "Apoptosis in cancer: from pathogenesis to treatment" 30 : 87-, 2011

      35 Sun SY, "Apoptosis as a novel target for cancer chemoprevention" 96 : 662-672, 2004

      36 Huang WH, "Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI" 70 : 2371-2380, 2006

      37 Zhu X, "Anticancer effects of Paris saponins by apoptosis and PI3K/AKT pathway in gefitinib-resistant non-small cell lung cancer" 22 : 1435-1441, 2016

      38 Yimam M, "Analgesic effects of a standardized bioflavonoid composition from Scutellaria baicalensis and Acacia catechu" 9 : 155-165, 2012

      39 Bhutani J, "Akt inhibitors: mechanism of action and implications for anticancer therapeutics" 8 : 49-, 2013

      40 Avisetti DR, "Activation of p38/JNK pathway is responsible for embelin induced apoptosis in lung cancer cells: transitional role of reactive oxygen species" 9 : e87050-, 2014

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2022 평가예정 재인증평가 신청대상 (재인증)
      2019-01-01 평가 등재학술지 선정 (계속평가) KCI등재
      2018-12-01 평가 등재후보로 하락 (계속평가) KCI등재후보
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2013-10-14 학술지명변경 외국어명 : Cancer Prevention Research -> Journal of Cancer Prevention KCI등재
      2012-10-15 학회명변경 영문명 : Korean Association of Cancer Prevention -> Korean Society of Cancer Preveniton KCI등재
      2011-04-04 학술지명변경 외국어명 : Journal of Korean Association of Cancer Prevention -> Cancer Prevention Research KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2008-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2007-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2005-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보

      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.22 0.22 0.18
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.15 0.12 0.405 0.13
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