Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells.

Cell cycle Cell proliferation Cyclin D GPCR VIPR2

Journal

Journal of pharmacological sciences
ISSN: 1347-8648
Titre abrégé: J Pharmacol Sci
Pays: Japan
ID NLM: 101167001

Informations de publication

Date de publication:
Mar 2024
Historique:
received: 01 11 2023
revised: 28 12 2023
accepted: 05 01 2024
medline: 24 2 2024
pubmed: 24 2 2024
entrez: 23 2 2024
Statut: ppublish

Résumé

Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate various downstream signaling molecules, such as protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K), and phospholipase C. In this study, we examined the role of VIPR2 in cell cycle progression. KS-133, a newly developed VIPR2-selective antagonist peptide, attenuated VIP-induced cell proliferation in MCF-7 cells. The percentage of cells in the S-M phase was decreased in MCF-7 cells treated with KS-133. KS-133 in the presence of VIP decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and glycogen synthase kinase-3β (GSK3β), resulting in a decrease in cyclin D1 levels. In MCF-7 cells stably-expressing VIPR2, KS-133 decreased PI3K activity and cAMP levels. Treatment with the ERK-specific kinase (MEK) inhibitor U0126 and the class I PI3K inhibitor ZSTK474 decreased the percentage of cells in the S phase. KS-133 reduced the percentage of cells in the S phase more than treatment with U0126 or ZSTK474 alone and did not affect the effect of the mixture of these inhibitors. Our findings suggest that VIPR2 signaling regulates cyclin D1 levels through the cAMP/PKA/ERK and PI3K/AKT/GSK3β pathways, and mediates the G1/S transition to control cell proliferation.

Identifiants

DOI: 10.1016/j.jphs.2024.01.002 PMID: 38395514
pubmed: 38395514
pii: S1347-8613(24)00002-1
doi: 10.1016/j.jphs.2024.01.002
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

139-147

Informations de copyright

Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest Kotaro Sakamoto is a full-time employee of Ichimaru Pharcos Co. Ltd. The authors declare that this study received funding from Ichimaru Pharcos Co. Ltd. The funder had the following involvement in the study: interpretation of data. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Auteurs

Satoshi Asano (S)

Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan; School of Dentistry, Hiroshima University, Hiroshima, 734-8553, Japan. Electronic address: sasano@hiroshima-u.ac.jp.

Ami Ono (A)

Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan; Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.

Kaede Baba (K)

School of Dentistry, Hiroshima University, Hiroshima, 734-8553, Japan.

Teru Uehara (T)

Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan; Department of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.

Kotaro Sakamoto (K)

Research & Development Department, Ichimaru Pharcos Company Limited, 318-1 Asagi, Motosu, Gifu, 501-0475, Japan.

Atsuko Hayata-Takano (A)

Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, 565-0871, Japan; Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Osaka, 565-0871, Japan.

Takanobu Nakazawa (T)

Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Laboratory of Molecular Biology, Department of Bioscience, Graduate School of Life Sciences, Tokyo University of Agriculture, Tokyo, 156-8502, Japan.

Souichi Yanamoto (S)

School of Dentistry, Hiroshima University, Hiroshima, 734-8553, Japan; Department of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.

Kotaro Tanimoto (K)

School of Dentistry, Hiroshima University, Hiroshima, 734-8553, Japan; Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan.

Hitoshi Hashimoto (H)

Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University, University of Fukui, Osaka, 565-0871, Japan; Division of Bioscience, Institute for Datability Science, Osaka University, Osaka, 565-0871, Japan; Transdimensional Life Imaging Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, 565-0871, Japan; Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.

Yukio Ago (Y)

Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8553, Japan; School of Dentistry, Hiroshima University, Hiroshima, 734-8553, Japan. Electronic address: yukioago@hiroshima-u.ac.jp.

Classifications MeSH