Fluvastatin is effective against thymic carcinoma.

Apoptosis / drug effects Cell Cycle / drug effects Cell Line, Tumor Fluvastatin / therapeutic use Humans Hydroxymethylglutaryl CoA Reductases / biosynthesis Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use Immunohistochemistry MAP Kinase Signaling System / drug effects Polyisoprenyl Phosphates / antagonists & inhibitors Prenylation / drug effects Thymoma / drug therapy Thymus Neoplasms / drug therapy
ERK Fluvastatin HMG-CoA reductase Isoprenylation Thymic carcinoma

Journal

Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521

Informations de publication

Date de publication:
01 Jan 2020
Historique:
received: 25 09 2019
revised: 21 11 2019
accepted: 26 11 2019
pubmed: 2 12 2019
medline: 14 1 2020
entrez: 2 12 2019
Statut: ppublish

Résumé

Thymic carcinoma is a rare epithelial tumor, for which, optimal pharmacotherapeutic methods have not yet been established. To develop new drug treatments for thymic carcinoma, we investigated the effects of fluvastatin-mediated pharmacological inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) on thymic carcinoma. Thymic carcinoma tissue was surgically excised and HMGCR expression was assessed by immunohistochemistry. Ty82 human thymic carcinoma cells were treated with fluvastatin (1-10 μM) and their growth was monitored. HMGCR was expressed on carcinoma cells but not on normal epithelial cells in thymic tissue. Inhibition of HMGCR by fluvastatin suppressed cell proliferation and induced the death of Ty-82 human thymic carcinoma cells. Fluvastatin mediated its antitumor effects by blocking the production of geranylgeranyl-pyrophosphate (GGPP), an isoprenoid that is produced from mevalonate and binds to small GTPases, which promotes cell proliferation. Fluvastatin showed marked antitumor effects on thymic carcinoma. The results suggest that the statin has clinical benefits in thymic carcinoma management.

Identifiants

DOI: 10.1016/j.lfs.2019.117110 PMID: 31786191
pubmed: 31786191
pii: S0024-3205(19)31037-9
doi: 10.1016/j.lfs.2019.117110
pii:
doi:

Substances chimiques

Hydroxymethylglutaryl-CoA Reductase Inhibitors 0
Polyisoprenyl Phosphates 0
Fluvastatin 4L066368AS
HMGCR protein, human EC 1.1.1.-
Hydroxymethylglutaryl CoA Reductases EC 1.1.1.-
geranylgeranyl pyrophosphate N21T0D88LX

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

117110

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Keitaro Hayashi (K)

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan. Electronic address: khayashi@dokkyomed.ac.jp.

Yoshimasa Nakazato (Y)

Department of Diagnostic Pathology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan.

Noriaki Morito (N)

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan.

Mizuki Sagi (M)

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan.

Tomoe Fujita (T)

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan.

Naohiko Anzai (N)

Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Shimotsuga, Japan; Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.

Masayuki Chida (M)

Department of General Thoracic Surgery, Dokkyo Medical University School of Medicine, Shimotsuga, Japan.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Cycle cellulaire › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Lipides › Acides gras › Acides heptanoïques › Fluvastatine › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › 3-Hydroxyacyl-CoA dehydrogenases › Hydroxymethylglutaryl-CoA reductases › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents régulateurs du métabolisme des lipides › Hypolipémiants › Anticholestérolémiants › Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Immunohistochimie › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Organophosphates › Polyisoprényl-phosphates › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Métabolisme › Prénylation › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Maladies lymphatiques › Tumeurs du thymus › Thymome › Fluvastatin is effective against thymic carcinoma.
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Maladies lymphatiques › Tumeurs du thymus › Fluvastatin is effective against thymic carcinoma.