Novel C-2 Aromatic Heterocycle-Substituted Triterpenoids Inhibit Hedgehog Signaling in GLI1 Overexpression Cancer Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73630900" target="_blank" >RIV/61989592:15640/25:73630900 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/25:73630900 RIV/61989592:15110/25:73630900 RIV/00098892:_____/25:10159217
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acsomega.4c11479" target="_blank" >https://pubs.acs.org/doi/10.1021/acsomega.4c11479</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acsomega.4c11479" target="_blank" >10.1021/acsomega.4c11479</a>
Alternative languages
Result language
angličtina
Original language name
Novel C-2 Aromatic Heterocycle-Substituted Triterpenoids Inhibit Hedgehog Signaling in GLI1 Overexpression Cancer Cells
Original language description
The hedgehog signaling pathway plays an important role in vertebrate embryonic development, tissue homeostasis, and tumorigenesis. Constitutive activation of Hh signaling in various human tumors leads to GLI-mediated transcription and tumor progression. Based on the preliminary screening of a large library of known triterpenes that exhibited interesting Hh inhibitory activity, we designed and synthesized a new series of triterpenoid analogues containing aromatic heterocyclic substituents at position C-2 to enhance their interference with Hh signaling. In this study, we evaluated the effect of 15 synthesized triterpenoids on cell proliferation and Hh pathway activity in relevant cancer cell lines. Among these compounds, two derivatives, 11a and 11b, both featuring a furan ring at position C-2, demonstrated potent inhibitory effects on proliferation and induced cell death in nonsmall cell lung cancer (NSCLC) and prostate cancer cell lines exhibiting hyper-activated Hh signaling. Moreover, these compounds significantly reduced GLI-mediated transcription in cell-based reporter assays. Detailed immunoblot analyses revealed that compounds 11a and 11b decreased the expression of endogenous GLI1 protein and its target genes associated with tumor progression and proliferation, such as Cyclin D1, N-Myc, and Bcl-2, in A549 and DU-145 cancer cells. These findings suggest that the antiproliferative effects of 11a and 11b are mediated through inhibition of the Hh signaling pathway and are promising candidates for the development of new anticancer therapies targeting Hh-dependent tumors.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
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)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Omega
ISSN
2470-1343
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
10617-10632
UT code for WoS article
001437040300001
EID of the result in the Scopus database
2-s2.0-105001076650