Triterpenoid derivatives inhibit Gli-mediated transcription in human glioblastoma cell line via direct interaction with Gli1

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73631651" target="_blank" >RIV/61989592:15640/25:73631651 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/25:73631651 RIV/61989592:15110/25:73631651

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0021925825023221?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0021925825023221?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2025.110472" target="_blank" >10.1016/j.jbc.2025.110472</a>

Result language

angličtina

Original language name

Triterpenoid derivatives inhibit Gli-mediated transcription in human glioblastoma cell line via direct interaction with Gli1

Original language description

The evolutionarily important Hedgehog (HH) signaling pathway plays a critical role in the development and progression of multiple solid tumors, such as basal cell carcinoma, medulloblastoma, rhabdomyosarcoma, and various gastrointestinal, pulmonary, and brain tumors. The proteins of the Gli (glioma-associated oncogene homologue) family are key mediators of the HH pathway. In the present study, we have focused on triterpenoid derivatives, which have been shown to induce apoptosis and inhibit HH signaling in rhabdomyosarcoma. Utilizing a U-87MG glioblastoma-derived reporter cell line, we screened a structurally diverse library of triterpenoid derivatives to identify potential antagonists of Gli-mediated transcription. We revealed two derivatives that not only selectively inhibited Gli-mediated gene transactivation but also displayed greater potency than the known Gli1 inhibitor GANT61. These compounds also demonstrated dose- and time-dependent inhibition of U-87MG tumor cell proliferation in vitro. Further mechanistic studies provided genetic evidence for the inhibition of the downstream HH pathway by these compounds, via reduced expression of Gli1 and its transcription targets. However, these compounds did not affect the ciliary localization of Smoothened (Smo). Our findings suggest that the observed inhibitory effects are likely due to a direct interaction between our compounds and Gli1.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Volume of the periodical

301

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

110472

UT code for WoS article

001565682800002

EID of the result in the Scopus database

2-s2.0-105014501810