2024
Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells
KRKOŠKA, Martin, Kamil PARUCH, Tereza ŠOŠOLÍKOVÁ, Gerardo VÁZQUEZ-GÓMEZ, Jarmila HERŮDKOVÁ et. al.Základní údaje
Originální název
Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells
Autoři
KRKOŠKA, Martin (203 Česká republika, domácí), Kamil PARUCH (203 Česká republika, domácí), Tereza ŠOŠOLÍKOVÁ (203 Česká republika, domácí), Gerardo VÁZQUEZ-GÓMEZ, Jarmila HERŮDKOVÁ (703 Slovensko), Jan NOVOTNÝ (203 Česká republika, domácí), Petra OVESNÁ (203 Česká republika, domácí), Petr SOVA a Alena HYRŠLOVÁ VACULOVÁ (203 Česká republika, garant)
Vydání
Biological Chemistry, Walter de Gruyter GmbH, 2024, 1431-6730
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30204 Oncology
Stát vydavatele
Německo
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 3.700 v roce 2022
Organizační jednotka
Přírodovědecká fakulta
UT WoS
001181919500001
Klíčová slova anglicky
checkpoint kinase 1; SCH900776; cisplatin; TRAIL; cell death; prostate cancer
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 26. 9. 2024 14:58, Mgr. Pavla Foltynová, Ph.D.
Anotace
V originále
Checkpoint kinase 1 (Chk1) plays an important role in regulation of the cell cycle, DNA damage response and cell death, and represents an attractive target in anticancer therapy. Small-molecule inhibitors of Chk1 have been intensively investigated either as single agents or in combination with various chemotherapeutic drugs and they can enhance the chemosensitivity of numerous tumor types. Here we newly demonstrate that pharmacological inhibition of Chk1 using potent and selective inhibitor SCH900776, currently profiled in phase II clinical trials, significantly enhances cytotoxic effects of the combination of platinum-based drugs (cisplatin or LA-12) and TRAIL (tumor necrosis factor-related apoptosis inducing ligand) in human prostate cancer cells. The specific role of Chk1 in the drug combination-induced cytotoxicity was confirmed by siRNA-mediated silencing of this kinase. Using RNAi-based methods we also showed the importance of Bak-dependent mitochondrial apoptotic pathway in the combined anticancer action of SCH900776, cisplatin and TRAIL. The triple drug combination-induced cytotoxicity was partially enhanced by siRNA-mediated Mcl-1 silencing. Our findings suggest that targeting Chk1 may be used as an efficient strategy for sensitization of prostate cancer cells to killing action of platinum-based chemotherapeutic drugs and TRAIL.
Návaznosti
EF16_025/0007381, projekt VaV |
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LM2023052, projekt VaV |
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