Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00601397" target="_blank" >RIV/68081707:_____/24:00601397 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/24:00081400 RIV/00216224:14310/24:00136147
Result on the web
<a href="https://www.degruyter.com/document/doi/10.1515/hsz-2023-0111/html" target="_blank" >https://www.degruyter.com/document/doi/10.1515/hsz-2023-0111/html</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1515/hsz-2023-0111" target="_blank" >10.1515/hsz-2023-0111</a>
Alternative languages
Result language
angličtina
Original language name
Inhibition of Chk1 stimulates cytotoxic action of platinum-based drugs and TRAIL combination in human prostate cancer cells
Original language description
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.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biological Chemistry
ISSN
1431-6730
e-ISSN
1437-4315
Volume of the periodical
405
Issue of the periodical within the volume
6
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
395-406
UT code for WoS article
001181919500001
EID of the result in the Scopus database
2-s2.0-85187403882