J 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.

Basic information

Original name

Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells

Authors

KRKOŠKA, Martin (203 Czech Republic, belonging to the institution), Kamil PARUCH (203 Czech Republic, belonging to the institution), Tereza ŠOŠOLÍKOVÁ (203 Czech Republic, belonging to the institution), Gerardo VÁZQUEZ-GÓMEZ, Jarmila HERŮDKOVÁ (703 Slovakia), Jan NOVOTNÝ (203 Czech Republic, belonging to the institution), Petra OVESNÁ (203 Czech Republic, belonging to the institution), Petr SOVA and Alena HYRŠLOVÁ VACULOVÁ (203 Czech Republic, guarantor)

Edition

Biological Chemistry, Walter de Gruyter GmbH, 2024, 1431-6730

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.700 in 2022

Organization unit

Faculty of Science

DOI

UT WoS

001181919500001

Keywords in English

checkpoint kinase 1; SCH900776; cisplatin; TRAIL; cell death; prostate cancer

Tags

International impact, Reviewed
Změněno: 26/9/2024 14:58, Mgr. Pavla Foltynová, Ph.D.

Abstract

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.

Links

EF16_025/0007381, research and development project
Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
LM2023052, research and development project
Name: Národní infrastruktura chemické biologie
Investor: Ministry of Education, Youth and Sports of the CR