Oridonin Induces a Caspase-Independent But Mitochondria- and MAPK-Dependent Cell Death in the Murine Fibrosarcoma Cell Line L929(Pharmacology)

スポンサーリンク

概要

• 論文の詳細を見る

• Oridonin, an active component isolated from Rabdosia rubescences, has been reported to exhibit antitumor effects, but little is known about its molecular mechanisms of action. In this study, the growth-inhibitory activity of oridonin for L929 cells is in time- and dose-dependent manner. After treatment with various concentrations of oridonin for 12 h, the majority of L929 cells underwent apoptosis as measured by an LDH activity-based assay. Although apoptotic bodies were observed in oridonin-treated L929 cells, DNA fragmentation as a hallmark of apoptosis was not found. The pan-caspase inhibitor, z-VAD, and caspase-3 inhibitor, z-DEVD, sensitized L929 cells to oridonin, however, a PART inhibitor (DPQ) effectively blocked oridonin-induced cell death. After 12 h treatment, PARP proenzyme was significantly cleaved. This result indicated that oridonin-induced L929 cell death required PARP degradation in a caspase-independent manner. In addition, an MEK/ERK inhibitor (PD98059) markedly blocked oridonin-induced cell death, whereas a p38 inhibitor (SB203580) and JNK inhibitor (SP600125) weakly protected the cells against death. Treatment with 41.2 μM oridonin for 12 h induced significant and persistent ERK activation and p38 inactivation in L929 cells without evident changes in the protein levels. The responsiveness of ERK and p38 to oridonin suggests the involvement of these kinases in this apoptotic process. Moreover, oridonin increased the ratio of Bax/Bcl-2 protein expression, whereas it had no effect on the expression of Bcl-xL. These results indicate that regulation of the Bcl-2 and MAPK families maybe the effector mechanisms of oridonin-induced L929 cell death, independent of the caspase pathway.

• 公益社団法人日本薬学会の論文
• 2004-10-01

著者

• Tashiro Shin-ichi

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• TASHIRO Shin-ichi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• ONODERA Satoshi

  Department of Clinical and Biomedical Sciences, Showa Pharmaceutical University

• Wu Li-jun

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Wu L

  Department Of Phytochemistry Shenyang Pharmaceutical University

• Onodera S

  Dep. Of Clinical And Biomedical Sciences Showa Pharmaceutical Univ. Jpn

• Ikejima Takashi

  China-japan Res. Inst. Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univ. Chn

• Tashiro Shin-ichi

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera Satoshi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Zhang Chun-ling

  China-japan Research Institute Of Medical And Pharmaceutical Sciences Shenyang Pharmaceutical Univer

• Tashiro Shin-ichi

  Department Of Cinical And Biomedical Sciences Showa Pharmaceutical University

• Tashiro S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• Onodera S

  Department Of Clinical And Biomedical Sciences Showa Pharmaceutical University

• IKEJIMA Takashi

  Department of Phytochemistry, Shenyang Pharmaceutical University

• Zhang Chun-Ling

  China–Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University

関連論文

• Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway
• 漢方薬はなぜ効くのか (特集 女性にやさしい漢方療法)
• 漢方薬はなぜ効くのか (特集 小児の漢方療法--エキス剤を使いこなそう) -- (漢方の基礎と薬効・その展開)
• The Protective Effect of Silibinin Against Mitomycin C-Induced Intrinsic Apoptosis in Human Melanoma A375-S2 Cells
• 大建中湯エキス製剤の使用実態と剤形に関する研究
• 単離灌流腎を用いたラット腎に対する五苓散の薬理効果に関する実験的検討
• 250 DJ(Docetaxel-Carboplatin)療法の背部痛に桂枝加朮附湯(TJ-18)が奏効した1例(53 運動器・整形外科(1))
• Bcl-2 Family Proteins Were Involved in Pseudolaric Acid B-Induced Autophagy in Murine Fibrosarcoma L929 Cells
• 24.天然薬物・健康食品などの生理活性の簡易評価方法 : アスコルビン酸の酸化に対する温度の影響(第77回日本医科器械学会大会一般演題講演集)
• 24 天然薬物・健康食品などの生理活性の簡易評価方法 : アスコルビン酸の酸化に対する温度の影響
• 26.電子スピン共鳴吸収スペクトル法(ESR)を用いた生薬の抽出温度による抽出成分のラジカル消去活性種の変化の検討
• 26 電子スピン共鳴吸収スペクトル法(ESR)を用いた生薬の抽出温度による抽出成分のラジカル消去活性種の変化の検討
• 演題番号:51 手指消毒薬による皮膚に及ぼす影響の評価法の検討
• 20. 電子スピン共鳴吸収スペクトル法(ESR)を用いた漢方薬のラジカル消去活性種の検討
• 妊娠時貧血と妊娠前の生活習慣との関係についての調査研究
• A Comparative Study of the Usefulness of Toki-shakuyaku-san and An Oral Iron Preparation in the Treatment of Hypochromic Anemia in Cases of Uterine Myoma
• P-70 甘草に起因する偽アルドステロン症の発症頻度に関する薬剤疫学的研究
• Caspase Inhibition Augmented Oridonin-Induced Cell Death in Murine Fibrosarcoma L929 by Enhancing Reactive Oxygen Species Generation
• Reactive Oxygen Species Mediate Oridonin-Induced HepG2 Apoptosis Through p53, MAPK, and Mitochondrial Signaling Pathways
• Inhibition of Insulin-like Growth Factor 1 Receptor Signaling Enhanced Silibinin-Induced Activation of Death Receptor and Mitochondrial Apoptotic Pathways in Human Breast Cancer MCF-7 Cells
• Oridonin Induced Autophagy in Human Cervical Carcinoma HeLa Cells Through Ras, JNK, and P38 Regulation
• Inactivation of Ras and Changes of Mitochondrial Membrane Potential Contribute to Oridonin-Induced Autophagy in A431 Cells
• Autophagy Preceded Apoptosis in Oridonin-Treated Human Breast Cancer MCF-7 Cells(Molecular and Cell Biology)
• Oridonin Inhibited the Tyrosine Kinase Activity and Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells(Molecular and Cell Biology)
• Oridonin-Induced A431 Cell Apoptosis Partially Through Blockage of the Ras/Raf/ERK Signal Pathway
• Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1
• Fibroblast Growth Factor-2 Suppresses Oridonin-Induced L929 Apoptosis Through Extracellular Signal-Regulated Kinase-Dependent and Phosphatidylinositol 3-Kinase-Independent Pathway
• Silibinin Protects Rat Cardiac Myocyte from Isoproterenol-Induced DNA Damage Independent on Regulation of Cell Cycle(Pharmacology)
• Fas/FasL Signaling Allows Extracelluar-Signal Regulated Kinase to Regulate Cytochrome c Release in Oridonin-Induced Apoptotic U937 Cells(Pharmacology)
• Augmentation of Oridonin-Induced Apoptosis Observed With Reduced Autophagy
• Silibinin Prevents UV-Induced HaCaT Cell Apoptosis Partly through Inhibition of Caspase-8 Pathway(Pharmacology)
• Bcl-2 Up-Regulation and P-p53 Down-Regulation Account for the Low Sensitivity of Murine L929 Fibrosarcoma Cells to Oridonin-Induced Apoptosis(Pharmacology)
• Activation of Phosphoinositide 3-Kinase, Protein Kinase C, and Extracellular Signal-Regulated Kinase Is Required for Oridonin-Enhanced Phagocytosis of Apoptotic Bodies in Human Macrophage-Like U937 Cells
• Evodiamine Induced Human Melanoma A375-S2 Cell Death Partially through Interleukin 1 Mediated Pathway(Pharmacology)
• (+)-Catechin, an Ingredient of Green Tea, Protects Murine Microglia From Oxidative Stress-Induced DNA Damage and Cell Cycle Arrest
• A Comparative Study of Laboratory Parameters and Symptoms Effected by Toki-shakuyaku-san and an Iron Preparation in Rats with Iron-Deficiency Anemia(Biopharmacy)
• Effects of Liver-Supplemented Food on the Development of Embryos in Mice
• Silibinin Activated p53 and Induced Autophagic Death in Human Fibrosarcoma HT1080 Cells via Reactive Oxygen Species-p38 and c-Jun N-Terminal Kinase Pathways
• O12-009 後発品使用促進の現状と問題点 : 後発医薬品は薬剤師に受け入れられているのか?(一般演題 口頭発表,糖尿病/使用状況調査・意識調査,医療薬学の創る未来 科学と臨床の融合)
• 軟骨細胞が合成するCOMP(Cartilage Oligomeric Matrix Protein)の性状解析
• S2-1 漢方薬はなぜ高齢者医療によいのか(高齢者医療と漢方薬,医療薬学の扉は開かれた)
• 漢方薬の薬理(生薬から漢方を考える,ワークショップ3,特別演題,第57回日本東洋医学会学術総会)
• 漢方臨床における漢方薬理(教育講演1-学術総会(57)基礎漢方講座5,特別演題,第57回日本東洋医学会学術総会)
• 2 症例に見る漢方薬理 : 適正な使用と服薬指導のために(第11回日本東洋医学会関東甲信越支部新潟県部会)
• Effect of Blended Ionomers on the Strain Hardening of Polyester-Type Elastomer/Ionomer Blends
• The relationship between 1-deoxynojirimycin content and α-glucosidase inhibitory activity in leaves of 276 mulberry cultivars (Morus spp.) of Kyoto, Japan
• Dynamic Responses to Acute Heat Stress between 34 ℃ and 38.5 ℃, and Characteristics of Heat Stress Response in Mice
• Increases in Plasma Dihydroxyphenylacetic Acid Levels in Decapitated Mice after Exposure to Various Stresses
• 和漢薬による糖尿病病態の改善
• 妊娠と出産における精油の安全性 (特集 周産期のアロマセラピー 基本のき)
• 薬理学からみた漢方薬の作用 (特集 女性のQOLと漢方)
• 会長講演 今,未病研究に要るもの--展望,方法論,そして技術と指標 (特集1 第10回日本未病システム学会論文集)
• Purification of a Noncollagenous High Molecular Weight Protein from Bovine Articular Cartilage
• Efficacy of Tokishakuyakusan on the Anemia in the Iron-Deficient Pregnant Rats(Biopharmacy)
• Expression of COMP and proteoglycan in the cartilage differentiation process of chondrocyte stem cell ATDC5 cell
• New Triterpenoids Isolated from the Root Bark of Ulmus pumila L.
• Dracorhodin Perchlorate Induces A375-S2 Cell Apoptosis via Accumulation of p53 and Activation of Caspases(Pharmacology)
• Cytotoxic Effects of Mansonone E and F Isolated from Ulmus pumila(Pharmacology)
• Dracorhodin Perchlorate Induces Apoptosis via Activation of Caspases and Generation of Reactive Oxygen Species
• Intracellular Regulation of Evodiamine-Induced A375-S2 Cell Death(Pharmacology)
• Roles of SIRT1 and Phosphoinositide 3-OH Kinase/Protein Kinase C Pathways in Evodiamine-Induced Human Melanoma A375-S2 Cell Death
• Roles of SIRT1 and Phosphoinositide 3-OH Kinase/Protein Kinase C Pathways in Evodiamine-Induced Human Melanoma A375-S2 Cell Death
• Trends in the prescriptions of Kampo medicines over a six-year period
• Oridonin Enhances Phagocytosis of UV-Irradiated Apoptotic U937 Cells(Pharmacology)
• Cytochrome c Release From Oridonin-Treated Apoptotic A375-S2 Cells Is Dependent on p53 and Extracellular Signal-Regulated Kinase Activation
• Oridonin Induces a Caspase-Independent But Mitochondria- and MAPK-Dependent Cell Death in the Murine Fibrosarcoma Cell Line L929(Pharmacology)
• Silymarin Prevents UV Irradiation-Induced A375-S2 Cell Apoptosis(Pharmacology)
• p53-Mediated Cell Cycle Arrest and Apoptosis Induced by Shikonin via a Caspase-9-Dependent Mechanism in Human Malignant Melanoma A375-S2 Cells
• Evodiamine, a constituent of Evodiae Fructus, induces anti-proliferating effects in tumor cells
• Pharmacological Properties of Traditional Medivines. XXV. Effects of Ephedrine, Amygdalin, Glycyrrhizin, Gypsum and Their Combinations on Body Temperature and Body Fluid
• Pharmacological Properties of Traditional Medicines. XXIV. Classification of Antiasthmatics Based on Constitutional Predispositions
• Pharmacoepidemiological study of the clinical efficacy of Sho-saiko-to (Xiao-Chai-Hu-Tang) in chronic liver disease patients
• Tumor-Stroma Interaction of Human Pancreatic Cancer : Acquired Resistance to Anticancer Drugs and Proliferation Regulation Is Dependent on Extracellular Matrix Proteins
• Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway
• Isolation and Immunochemical Characterization of Heparan Sulfate Rich Proteoglycan (HSPG) Present in the Basement Membrane of Human Placenta
• TNFα-Induced Necroptosis and Autophagy via Supression of the p38–NF-κB Survival Pathway in L929 Cells
• 植物香気成分の示す多様な作用とその臨床応用(講座:香気成分の化学 1)
• TNFα-Induced Necroptosis and Autophagy via Supression of the p38-NF-κB Survival Pathway in L929 Cells
• Activation of ERK-p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells
• Interruption of Hepatocyte Growth Factor Signaling Augmented Oridonin-Induced Death in Human Non-small Cell Lung Cancer A549 Cells via c-Met-Nuclear Factor-κB-Cyclooxygenase-2 and c-Met-Bcl-2-Caspase-3 Pathways
• Activated O_2^ and H_2O_2 Mediated Cell Survival in SU11274-Treated Non-Small-Cell Lung Cancer A549 Cells via c-Met-PI3K-Akt and c-Met-Grb2/SOS-Ras-p38 Pathways
• Activated O2•− and H2O2 Mediated Cell Survival in SU11274-Treated Non-Small-Cell Lung Cancer A549 Cells via c-Met–PI3K–Akt and c-Met–Grb2/SOS–Ras–p38 Pathways
• Dracorhodin Perchlorate Induces Apoptosis via Activation of Caspases and Generation of Reactive Oxygen Species
• Hydroxyl Radical (·OH) Played a Pivotal Role in Oridonin-Induced Apoptosis and Autophagy in Human Epidermoid Carcinoma A431 Cells
• 臨床から学ぶ医療薬学(22)透析患者への投薬
• Pseudolaric Acid B–Induced Autophagy Contributes to Senescence via Enhancement of ROS Generation and Mitochondrial Dysfunction in Murine Fibrosarcoma L929 Cells
• 臨床から学ぶ医療薬学(24・完)腹痛から考えること(2)
• Pseudolaric Acid B-Induced Autophagy Contributes to Senescence via Enhancement of ROS Generation and Mitochondrial Dysfunction in Murine Fibrosarcoma L929 Cells

もっと見る 閉じる

スポンサーリンク