HMG-CoA reductase degrader, SR-12813, counteracts statin-induced upregulation of HMG-CoA reductase and augments the anticancer effect of atorvastatin.

Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Atorvastatin / pharmacology Up-Regulation Hydroxymethylglutaryl CoA Reductases / genetics
Cancer cell Dual inhibition HMGCR SR-12813 Statin Targeted protein degradation

Journal

Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516

Informations de publication

Date de publication:
15 10 2023
Historique:
received: 06 06 2023
revised: 18 07 2023
accepted: 26 07 2023
medline: 4 9 2023
pubmed: 5 8 2023
entrez: 4 8 2023
Statut: ppublish

Résumé

Statins are cholesterol-lowering drugs that have exhibited potential as cancer therapeutic agents. However, as some cancer cells are resistant to statins, broadening an anticancer spectrum of statins is desirable. The upregulated expression of the statin target enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase (HMGCR), in statin-treated cancer cells is a well-known mechanism of statin resistance, which can be counteracted by the downregulation of HMGCR gene expression, or degradation of the HMGCR protein. However, the mechanism by which HMGCR degradation influences the anticancer effects of statins remain unreported. We tested the effect of the HMGCR degrader compound SR-12813 at a concentration that did not affect the growth of eight diverse tumor cell lines. Combined treatment with atorvastatin and a low concentration of SR-12813 led to lowering of increased HMGCR expression, and augmented the cytostatic effect of atorvastatin in both statin-resistant and -sensitive cancer cells compared with that of atorvastatin treatment alone. Dual-targeting of HMGCR using statins and SR-12813 (or similar compounds) could provide an improved anticancer therapeutic approach.

Identifiants

DOI: 10.1016/j.bbrc.2023.07.056 PMID: 37541087
pubmed: 37541087
pii: S0006-291X(23)00928-2
doi: 10.1016/j.bbrc.2023.07.056
pii:
doi:

Substances chimiques

Hydroxymethylglutaryl-CoA Reductase Inhibitors 0
Atorvastatin A0JWA85V8F
3-hydroxy-3-methylglutaryl-coenzyme A 1553-55-5
SR 12813 0
Hydroxymethylglutaryl CoA Reductases EC 1.1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13-19

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no potential competing interests.

Auteurs

Yaxuan Zhou (Y)

Graduate School of Science and Technology, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo, 669-1330, Japan.

Jiro Tashiro (J)

Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University, 4-101 Koyama Minami, Tottori, Tottori, 680-8553, Japan.

Shiori Kamatani (S)

Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University, 4-101 Koyama Minami, Tottori, Tottori, 680-8553, Japan.

Nanami Irie (N)

Graduate School of Science and Technology, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo, 669-1330, Japan.

Akito Suzuki (A)

Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University, 4-101 Koyama Minami, Tottori, Tottori, 680-8553, Japan.

Takuro Ishikawa (T)

Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.

Katsuhiko Warita (K)

Department of Veterinary Anatomy, School of Veterinary Medicine, Tottori University, 4-101 Koyama Minami, Tottori, Tottori, 680-8553, Japan. Electronic address: waritak@tottori-u.ac.jp.

Zoltán N Oltvai (ZN)

Department of Pathology and Laboratory Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY, 14642, USA. Electronic address: Zoltan_Oltvai@URMC.Rochester.edu.

Tomoko Warita (T)

Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo, 669-1330, Japan.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents régulateurs du métabolisme des lipides › Hypolipémiants › Anticholestérolémiants › Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase › HMG-CoA reductase degrader, SR-12813,...
questionsmedicales.fr › Lipides › Acides gras › Acides heptanoïques › Atorvastatine › HMG-CoA reductase degrader, SR-12813,...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › HMG-CoA reductase degrader, SR-12813,...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › NAD (+) and NADP (+) dependent Alcohol oxidoreductases › 3-Hydroxyacyl-CoA dehydrogenases › Hydroxymethylglutaryl-CoA reductases › HMG-CoA reductase degrader, SR-12813,...