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@article{1389199,
author = {Herůdková, Jarmila and Paruch, Kamil and Khirsariya, PrashantKumar and Souček, Karel and Krkoška, Martin and Vondálová Blanářová, Olga and Sova, Petr and Kozubík, Alois and Hyršlová Vaculová, Alena},
article_location = {New York},
article_number = {10},
doi = {http://dx.doi.org/10.1016/j.neo.2017.08.002},
keywords = {Chk1 Inhibitor SCH900776},
language = {eng},
issn = {1476-5586},
journal = {Neoplasia},
title = {Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells},
url = {https://doi.org/10.1016/j.neo.2017.08.002},
volume = {19},
year = {2017}
}
TY - JOUR
ID - 1389199
AU - Herůdková, Jarmila - Paruch, Kamil - Khirsariya, PrashantKumar - Souček, Karel - Krkoška, Martin - Vondálová Blanářová, Olga - Sova, Petr - Kozubík, Alois - Hyršlová Vaculová, Alena
PY - 2017
TI - Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells
JF - Neoplasia
VL - 19
IS - 10
SP - 830-841
EP - 830-841
PB - ELSEVIER SCIENCE INC
SN - 14765586
KW - Chk1 Inhibitor SCH900776
UR - https://doi.org/10.1016/j.neo.2017.08.002
N2 - Although Chk1 kinase inhibitors are currently under clinical investigation as effective cancer cell sensitizers to the cytotoxic effects of numerous chemotherapeutics, there is still a considerable uncertainty regarding their role in modulation of anticancer potential of platinum-based drugs. Here we newly demonstrate the ability of one of the most specific Chk1 inhibitors, SCH900776 (MK-8776), to enhance human colon cancer cell sensitivity to the cytotoxic effects of platinum(II) cisplatin and platinum(IV)- LA-12 complexes. The combined treatment with SCH900776 and cisplatin or LA-12 results in apparent increase in G1/S phase–related apoptosis, stimulation of mitotic slippage, and senescence of HCT116 cells. We further show that the cancer cell response to the drug combinations is significantly affected by the p21, p53, and PTEN status. In contrast to their wt counterparts, the p53- or p21-deficient cells treated withSCH900776 and cisplatin or LA-12 enter mitosis and become polyploid, and the senescence phenotype is strongly suppressed. While the cell death induced by SCH900776 and cisplatin or LA-12 is significantly delayed in the absence of p53, the anticancer action of the drug combinations is significantly accelerated in p21-deficient cells,which is associated with stimulation of apoptosis beyond G2/ Mcell cycle phase.Wealso show that cooperative killing action of the drug combinations in HCT116 cells is facilitated in the absence ofPTEN. Our results indicate that SCH900776mayact as an importantmodulator of cytotoxic response triggered by platinum-based drugs in colon cancer cells.
ER -
HERŮDKOVÁ, Jarmila, Kamil PARUCH, PrashantKumar KHIRSARIYA, Karel SOUČEK, Martin KRKOŠKA, Olga VONDÁLOVÁ BLANÁŘOVÁ, Petr SOVA, Alois KOZUBÍK and Alena HYRŠLOVÁ VACULOVÁ. Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells. \textit{Neoplasia}. New York: ELSEVIER SCIENCE INC, 2017, vol.~19, No~10, p.~830-841. ISSN~1476-5586. Available from: https://dx.doi.org/10.1016/j.neo.2017.08.002.
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