Počet záznamů: 1
STAT3 inhibitor Stattic and its analogues inhibit STAT3 phosphorylation and modulate cytokine secretion in senescent tumour cells
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SYSNO ASEP 0571758 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název STAT3 inhibitor Stattic and its analogues inhibit STAT3 phosphorylation and modulate cytokine secretion in senescent tumour cells Tvůrce(i) Mikyšková, Romana (UMG-J) RID
Sapega, Olena (UMG-J)
Psotka, M. (CZ)
Novotný, Ondřej (UMG-J) ORCID
Hodný, Zdeněk (UMG-J) RID
Bálintová, Soňa (UMG-J)
Malinak, D. (CZ)
Svobodová, J. (CZ)
Andrýs, R. (CZ)
Ryšánek, David (UMG-J)
Musílek, K. (CZ)
Reiniš, Milan (UMG-J) RIDCelkový počet autorů 12 Číslo článku 81 Zdroj.dok. Molecular Medicine Reports. - : Spandidos Publications - ISSN 1791-2997
Roč. 27, č. 4 (2023)Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. GR - Řecko Klíč. slova cellular senescence ; docetaxel ; signal transducer and activator of transcription 3 inhibition ; Stattic ; senescence-associated secretory phenotype Obor OECD Immunology CEP LX22NPO5102 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy NV18-05-00562 GA MZd - Ministerstvo zdravotnictví Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000949329600001 EID SCOPUS 85148835206 DOI 10.3892/mmr.2023.12968 Anotace 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. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2024 Elektronická adresa https://www.spandidos-publications.com/10.3892/mmr.2023.12968
Počet záznamů: 1