Inhibition of Autophagy Enhances Sunitinib-Induced Cytotoxicity in Rat Pheochromocytoma PC12 cells
スポンサーリンク
概要
- 論文の詳細を見る
Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with antiangiogenic and antitumor activity that mainly targets vascular endothelial growth factor receptors, and recently, it has been shown to be an active agent for the treatment of malignant pheochromocytomas. Previously, we demonstrated that sunitinib directly inhibited mTORC1 signaling in rat pheochromocytoma PC12 cells. Although autophagy is a highly regulated cellular process, its relevance to cancer seems to be complicated. It is of note that inhibition of mTORC1 is a prerequisite for autophagy induction. Indeed, direct mTORC1 inhibition initiates ULK1/2 autophosphorylation and subsequent Atg13 and FIP200 phosphorylation, inducing autophagy. Here, we demonstrated that sunitinib significantly increased the levels of LC3-II, concomitant with a decrease of p62 in PC12 cells. Following sunitinib treatment, immunofluorescent imaging revealed a marked increased punctate LC3-II distribution. Furthermore, <I>Atg13</I> knockdown significantly reduced its protein level, which in turn abolished sunitinib-induced autophagy. Moreover, inhibition of autophagy by siRNAs targeting <I>Atg13</I> or by pharmacological inhibition with ammonium chloride, enhanced both sunitinib-induced apoptosis and anti-proliferation. Thus, sunitinib-induced autophagy is dependent on the suppression of mTORC1 signaling and the formation of ULK1/2–Atg13–FIP200 complexes. Inhibition of autophagy may be a promising therapeutic option for improving the anti-tumor effect of sunitinib.
著者
-
Shimano Hitoshi
Department Of Internal Medicine (endocrinology And Metabolism) Graduate School Of Comprehensive Huma
-
TAKEKOSHI KAZUHIRO
Department of Clinical Pathology, University of Tsukuba
-
Kawakami Yasushi
Department Of Biology Faculty Of Education Tottori University:(present Address)tottori West Technica
-
Ikeda Tatsuhiko
Department Of Biotechnology Graduate School Of Engineering Osaka University
-
Miura Masahiro
Departmemt Of Chemistiy Graduate School Of Science Kobe University
-
HARA Hisato
Department of Breast Thyroid Endocrine Surgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, Tsukuba University
-
Hara Hisato
Department of Endocrine Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
Ishii Kiyo-aki
Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
Saito Yuria
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
Otagiri Aoi
Department of Endocrine Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
Takekoshi Kazuhiro
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
Kawakami Yasushi
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
-
ISHII Kiyo-aki
Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba
-
OTAGIRI Aoi
Department of Endocrine Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba
関連論文
- DrEFTIR : The data mining software for fourier transform near-infrared reflectance spectroscopy focused on food metabolic finger printing
- SPARC is a Major Secretory Gene Expressed and Involved in the Development of Proliferative Diabetic Retinopathy
- Identification of ISG12b as a Putative Interferon-inducible Adipocytokine which is Highly Expressed in White Adipose Tissue
- Distinct Effects of Pravastatin, Atorvastatin, and Simvastatin on Insulin Secretion from a β-cell Line, MIN6 Cells
- Effects of Atorvastatin on Glucose Metabolism and Insulin Resistance in KK/Ay Mice
- Cerebral Hemorrhagic Infarction after Radiation for Pituitary Adenoma
- A Kindred of Familial Acromegaly without Evidence for Linkage to MEN-1 Locus
- Proposed Guidelines for Hypertriglyceridemia in Japan with Non-HDL Cholesterol as the Second Target
- Iridium-Catalyzed Reaction of 1-Naphthols, N-(1-Naphthyl)benzenesulfonamides, and Salicylaldehyde with Internal Alkynes
- Palladium-Catalyzed Cross-Coupling of Benzyl Ketones and α,β-Unsaturated Carbonyl and Phenolic Compounds with ο-Dibromobenzenes to Produce Cyclic Products
- Mulple Arylation of Phenols around the Oxygen under Palladium Catalysis
- Iridium-Catalyzed Regioselective Reaction of 1-Naphthols with Alkynes at the peri-Position
- Regioselective Arylation Reactions of Bipheny1-2-ols, Naphthols, and Benzylic Compounds with Aryl Halides under Palladium Catalysis
- Palladium-Catalyzed Arylation of 2,6-Di-tert-butylphenol with Aryl Bromides to Produce 1,1'-Biphenyl-4-ol Derivatives
- Palladium-Catalyzed Arylation of Azole Compounds with Aryl Halides in the Presence of Alkali Metal Carbonates and the Use of Copper Iodide in the Reaction
- Palladium-Catalyzed Oxidative Cross-Coupling of 2-Phenylphenols with Alkenes
- Palladium-Catalyzed Reaction of Aryl Bromides with Dialkylacetylenes to Produce Allenic Compounds
- Palladium-Catalyzed Coupling Reaction of Salicylaldehydes with Aryl Iodides via Cleavage of the Aldehyde C-H Bond
- Ultrasonographic Features of Parathyroid Carcinoma
- Non-Invasive Lobular Carcinoma within a Fibroadenoma, a Preoperatively Diagnosed Case
- Interventricular Methotrexate Therapy for Carcinomatous Meningitis due to Breast Cancer: A Case with Leukoencephalopathy
- Reaction of 2-Hydroxybenzaldehydes with Alkynes, Alkenes, or Allenes via Cleavage of the Aldehyde C-H Bond Using a Rhodium Catalyst System
- Effects of Pitavastatin (LIVALO Tablet) on High Density Lipoprotein Cholesterol (HDL-C) in Hypercholesterolemia : Sub-Analysis of LIVALO Effectiveness and Safety (LIVES) Study
- Benzene Toxicity and Yield Improvement in a cis-Benzeneglycol Production Process
- cis-Benzeneglycol Production Using a Mutant Pseudomonas Strain
- Expression of the Human Telomerase Reverse Transcriptase in Pheochromocytoma and Neuroblastoma Tissues
- Cerebral Metastasis of Parathyroid Carcinoma : Case Report
- 寄生性線虫類の両性イオン型糖脂質(1)ブタカイチュウ(Ascaris suum)のN-アセチルグルコサミン-6-ホスホコリン含有スフィンゴ糖脂質群の化学構造
- Catalytic Aryl-Aryl Coupling via Cleavage of C-H or C-C Bond
- Inhibition of Electron Acceptance from Ascorbate by the Specific N-carbethoxylations of Maize Cytochrome b_ : A Common Mechanism for the Transmembrane Electron Transfer in Cytochrome b_ Protein Family
- 3P110 Direct electrochemical analyses of cytochromes b5 with a mutated heme pocket at a gold electrode modified with β-mercaptopropionic acid(Heme proteins,The 48th Annual Meeting of the Biophysical Society of Japan)
- Pyrite Oxidation by Sulfolobus acidocaldarius
- Rhodium-catalyzed Selective Cross-coupling of Internal Alkynes with a Terminal Silylacetylene
- Formate Dehydrogenase Gene of Arabidopsis thaliana is Induced by Formaldehyde and Not by Formic Acid
- Fucoxanthin, an antioxidative substance from marine diatom Phaeodactylum tricornutum
- Geographic Variation of the Brachypterous Grasshopper Parapodisma setouchiensis Group in Western Honshu, with Its Taxonomic Revision
- Inhibition of Denitritification by Oxygen in Paracoccus denitrificans
- A Case of Mid-Trimester Intrauterine Fetal Death with Cushing's Syndrome
- Rhodium-catalyzed Oxidative Coupling/Cyclization of Benzamides with Alkynes via C-H Bond Cleavage
- Synthesis of Substituted Stilbenes via Direct Decarboxylative Coupling of Cinnamic Acids with Arylboronic Acids under Palladium Catalysis
- Rhodium-catalyzed and Coordination-assisted Regioselective Alkenylation of Aromatic C-H Bonds with Terminal Silylacetylenes
- Synthesis of Alkylated Benzo[2,1-b:3,4-b']dithiophenes by Annulative Coupling and Their Direct Arylation under Palladium Catalysis
- Difference in abundance of blood and lymphatic capillaries in the murine epididymis
- Copper-Promoted Reaction of Aryl Iodides with Activated Methine Compounds
- Catalytic Direct Arylation of Heteroaromatic Compounds
- A Facile Transformation of Arabidopsis thaliana Using Ceramic Supported Propagation System
- Rhodium-catalyzed Oxidative Coupling of Benzylamines with Alkynes through Dehydrogenation and Dehydrogenative Cyclization
- Palladium Nanoparticles in Ionic Liquid by Sputter Deposition as Catalysts for Suzuki-Miyaura Coupling in Water
- Lymphatic Drainage of the Cerebrospinal Fluid from Monkey Spinal Meninges with Special Reference to the Distribution of the Epidural Lymphatics
- Ruthenium-catalyzed Oxidative Alkenylation of Arenes via Regioselective C-H Bond Cleavage Directed by a Nitrogen-containing Group
- Interaction of modified tail-anchored proteins with liposomes : Effect of extensions of hydrophilic segment at the COOH-terminus of holo-cytochromes b_5(ENZYMOLOGY, PROTEIN ENGINEERING, AND ENZYME TECHNOLOGY)
- Palladium-catalyzed Direct Monoarylation of Thiophene-, Benzothiophene-, and Indoleacetic Acids through Regioselective C-H Bond Cleavage
- Ru/Ag-Catalyzed Oxidative Alkenylation of Benzamides and Phenylazoles through Regioselective C-H Bond Cleavage
- Interaction of modified tail-anchored proteins with liposomes : Effect of extensions of hydrophilic segment at the COOH-terminus of holo-cytochromes b_5
- Inhibition of Autophagy Enhances Sunitinib-Induced Cytotoxicity in Rat Pheochromocytoma PC12 cells
- Even Low-Intensity and Low-Volume Exercise Training May Improve Insulin Resistance in the Elderly
- Tracheomalacia after reoperation for an adenomatous goiter located in a unique position
- Nutrient limitations on biodegradation of n-hexadecane by Bacillus sp., a candidate organism in seeding.
- Inhibition of Autophagy Enhances Sunitinib-Induced Cytotoxicity in Rat Pheochromocytoma PC12 cells
- Plasma free metanephrines in the diagnosis of pheochromocytoma: diagnostic accuracy and strategies for Japanese patients
- Rhodium–Catalyzed Intramolecular Dehydrogenative Aryl–Aryl Coupling Using Air as Terminal Oxidant
- Formal anti-Markovnikov Hydroamination of Terminal Aryl Alkynes with Pinacolborane and Hydroxylamines via Zr/Cu Sequential Catalysis