Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic
Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon
Cancer Cells

J 2017

Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells

HERŮDKOVÁ, Jarmila, Kamil PARUCH, PrashantKumar KHIRSARIYA, Karel SOUČEK, Martin KRKOŠKA et. al.

Basic information

Original name

Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells

Authors

HERŮDKOVÁ, Jarmila (703 Slovakia, belonging to the institution), Kamil PARUCH (203 Czech Republic, guarantor, belonging to the institution), PrashantKumar KHIRSARIYA (356 India, belonging to the institution), Karel SOUČEK (203 Czech Republic, belonging to the institution), Martin KRKOŠKA (203 Czech Republic, belonging to the institution), Olga VONDÁLOVÁ BLANÁŘOVÁ (203 Czech Republic), Petr SOVA (203 Czech Republic), Alois KOZUBÍK (203 Czech Republic, belonging to the institution) and Alena HYRŠLOVÁ VACULOVÁ (203 Czech Republic)

Edition

Neoplasia, New York, ELSEVIER SCIENCE INC, 2017, 1476-5586

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10401 Organic chemistry

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.994

RIV identification code

RIV/00216224:14310/17:00097522

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.neo.2017.08.002

UT WoS

000411874100009

Keywords in English

Chk1 Inhibitor SCH900776

Abstract

V originále

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.

Links

LM2015063, research and development project

Name: Národní infrastruktura chemické biologie (Acronym: CZ-OPENSCREEN)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

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. 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.

@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.

Detailed Information on Publication Record