Drug development targeting the glycogen synthase kinase-3/β (GSK-3/β)-mediated signal transduction pathway: Inhibitors of the Wnt//β-catenin signaling pathway as novel anticancer drugs

Fumi Takahashi, Toshiyuki Sasaguri

Research output: Contribution to journalShort survey

56 Citations (Scopus)

Abstract

Accumulating evidence suggests that the Wnt/β-catenin signaling pathway is often involved in oncogenesis and cancer development. Accordingly, a novel anticancer drug can be developed using inhibitors of this pathway. However, at present, there is no selective inhibitor of this pathway available as a therapeutic agent. Although all the components of the Wnt/β-catenin signaling pathway can be a target for drug development, glycogen synthase kinase-3? (GSK-3β), in particular, may be a good target because GSK-β? is an essential component of the pathway, and activation of this kinase results in the inhibition of the Wnt signaling pathway. We found that the differentiation-inducing factors (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/β-catenin signaling pathway via the activation of GSK-3β, resulting in the cell- cycle arrest of human cancer cell lines. In this review, we summarize our recent findings on the antiproliferative effect of DIFs and show the possibility for development of a novel anticancer drug from DIFs and their derivatives.

Original languageEnglish
Pages (from-to)179-183
Number of pages5
JournalJournal of Pharmacological Sciences
Volume109
Issue number2
DOIs
Publication statusPublished - Jun 22 2009

Fingerprint

Glycogen Synthase Kinase 3
Catenins
Wnt Signaling Pathway
Drug Delivery Systems
Signal Transduction
Pharmaceutical Preparations
Dictyostelium
Cell Cycle Checkpoints
Neoplasms
Carcinogenesis
Phosphotransferases
Cell Line
1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

@article{1a48f0605c1b4337b15359063ecf4385,
title = "Drug development targeting the glycogen synthase kinase-3/β (GSK-3/β)-mediated signal transduction pathway: Inhibitors of the Wnt//β-catenin signaling pathway as novel anticancer drugs",
abstract = "Accumulating evidence suggests that the Wnt/β-catenin signaling pathway is often involved in oncogenesis and cancer development. Accordingly, a novel anticancer drug can be developed using inhibitors of this pathway. However, at present, there is no selective inhibitor of this pathway available as a therapeutic agent. Although all the components of the Wnt/β-catenin signaling pathway can be a target for drug development, glycogen synthase kinase-3? (GSK-3β), in particular, may be a good target because GSK-β? is an essential component of the pathway, and activation of this kinase results in the inhibition of the Wnt signaling pathway. We found that the differentiation-inducing factors (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/β-catenin signaling pathway via the activation of GSK-3β, resulting in the cell- cycle arrest of human cancer cell lines. In this review, we summarize our recent findings on the antiproliferative effect of DIFs and show the possibility for development of a novel anticancer drug from DIFs and their derivatives.",
author = "Fumi Takahashi and Toshiyuki Sasaguri",
year = "2009",
month = "6",
day = "22",
doi = "10.1254/jphs.08R28FM",
language = "English",
volume = "109",
pages = "179--183",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8613",
publisher = "Japanese Pharmacological Society",
number = "2",

}

TY - JOUR

T1 - Drug development targeting the glycogen synthase kinase-3/β (GSK-3/β)-mediated signal transduction pathway

T2 - Inhibitors of the Wnt//β-catenin signaling pathway as novel anticancer drugs

AU - Takahashi, Fumi

AU - Sasaguri, Toshiyuki

PY - 2009/6/22

Y1 - 2009/6/22

N2 - Accumulating evidence suggests that the Wnt/β-catenin signaling pathway is often involved in oncogenesis and cancer development. Accordingly, a novel anticancer drug can be developed using inhibitors of this pathway. However, at present, there is no selective inhibitor of this pathway available as a therapeutic agent. Although all the components of the Wnt/β-catenin signaling pathway can be a target for drug development, glycogen synthase kinase-3? (GSK-3β), in particular, may be a good target because GSK-β? is an essential component of the pathway, and activation of this kinase results in the inhibition of the Wnt signaling pathway. We found that the differentiation-inducing factors (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/β-catenin signaling pathway via the activation of GSK-3β, resulting in the cell- cycle arrest of human cancer cell lines. In this review, we summarize our recent findings on the antiproliferative effect of DIFs and show the possibility for development of a novel anticancer drug from DIFs and their derivatives.

AB - Accumulating evidence suggests that the Wnt/β-catenin signaling pathway is often involved in oncogenesis and cancer development. Accordingly, a novel anticancer drug can be developed using inhibitors of this pathway. However, at present, there is no selective inhibitor of this pathway available as a therapeutic agent. Although all the components of the Wnt/β-catenin signaling pathway can be a target for drug development, glycogen synthase kinase-3? (GSK-3β), in particular, may be a good target because GSK-β? is an essential component of the pathway, and activation of this kinase results in the inhibition of the Wnt signaling pathway. We found that the differentiation-inducing factors (DIFs), putative morphogens for Dictyostelium discoideum, inhibit the Wnt/β-catenin signaling pathway via the activation of GSK-3β, resulting in the cell- cycle arrest of human cancer cell lines. In this review, we summarize our recent findings on the antiproliferative effect of DIFs and show the possibility for development of a novel anticancer drug from DIFs and their derivatives.

UR - http://www.scopus.com/inward/record.url?scp=65449133183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65449133183&partnerID=8YFLogxK

U2 - 10.1254/jphs.08R28FM

DO - 10.1254/jphs.08R28FM

M3 - Short survey

C2 - 19179804

AN - SCOPUS:65449133183

VL - 109

SP - 179

EP - 183

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

SN - 1347-8613

IS - 2

ER -