STAT3 inhibitor Stattic and its analogues inhibit STAT3 phosphorylation and modulate cytokine secretion in senescent tumour cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F23%3A50020359" target="_blank" >RIV/62690094:18470/23:50020359 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/23:00571758

Result on the web

<a href="https://www.spandidos-publications.com/10.3892/mmr.2023.12968" target="_blank" >https://www.spandidos-publications.com/10.3892/mmr.2023.12968</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/mmr.2023.12968" target="_blank" >10.3892/mmr.2023.12968</a>

Result language

angličtina

Original language name

STAT3 inhibitor Stattic and its analogues inhibit STAT3 phosphorylation and modulate cytokine secretion in senescent tumour cells

Original language description

Signal transducer and activator of transcription 3 (STAT3) signalling serves an important role in carcinogenesis and cellular senescence, and its inhibition in tumour cells represents an attractive therapeutic target. Premature cellular senescence, a process of permanent proliferative arrest of cells in response to various inducers, such as cytostatic drugs or ionizing radiation, is accompanied by morphological and secretory changes, and by altered susceptibility to chemotherapeutic agents, which can thereby complicate their eradication by cancer therapies. In the present study, the responsiveness of proliferating and docetaxel (DTX)-induced senescent cancer cells to small molecule STAT3 inhibitor Stattic and its analogues was evaluated using tumour cell lines. These agents displayed cytotoxic effects in cell viability assays on both proliferating and senescent murine TRAMP-C2 and TC-1 cells; however, senescent cells were markedly more resistant. Western blot analysis revealed that Stattic and its analogues effectively inhibited constitutive STAT3 phosphorylation in both proliferating and senescent cells. Furthermore, whether the Stattic-derived inhibitor K1836 could affect senescence induction or modulate the phenotype of senescent cells was evaluated. K1836 treatment demonstrated no effect on senescence induction by DTX. However, the K1836 compound significantly modulated secretion of certain cytokines (interleukin-6, growth-regulated oncogene alpha and monocyte chemoattractant protein-1). In summary, the present study demonstrated differences between proliferating and senescent tumour cells in terms of their susceptibility to STAT3 inhibitors and demonstrated the ability of the new STAT3 inhibitor K1836 to affect the secretion of essential components of the senescence-associated secretory phenotype. The present study may be useful for further development of STAT3 inhibitor-based therapy of cancer or age-related diseases.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30107 - Medicinal chemistry

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

2023

Confidentiality

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

Name of the periodical

Molecular Medicine Reports

ISSN

1791-2997

e-ISSN

1791-3004

Volume of the periodical

27

Issue of the periodical within the volume

4

Country of publishing house

GR - GREECE

Number of pages

10

Pages from-to

"Article Number: 81"

UT code for WoS article

000949329600001

EID of the result in the Scopus database

2-s2.0-85148835206