Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon
Exposure to Cisplatin

J 2019

Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin

PEŠKOVÁ, Lucie, Vladimír VINARSKÝ, Tomáš BÁRTA and Aleš HAMPL

Basic information

Original name

Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin

Authors

PEŠKOVÁ, Lucie (203 Czech Republic, belonging to the institution), Vladimír VINARSKÝ (203 Czech Republic, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution) and Aleš HAMPL (203 Czech Republic, guarantor, belonging to the institution)

Edition

Stem Cells International, London, HINDAWI LTD, 2019, 1687-966X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.869

RIV identification code

RIV/00216224:14110/19:00108504

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1155/2019/4279481

UT WoS

000482101000001

Keywords in English

APOPTOSIS-INDUCING LIGAND; ANTITUMOR-ACTIVITY; CARCINOMA CELLS; DNA; DEATH; DIFFERENTIATION; COMBINATION; ACTIVATION; CASPASE-10; RECEPTORS

Abstract

V originále

Tumor necrosis factor-related apoptosis-inducing ligand-TRAIL-is a protein operating as a ligand capable of inducing apoptosis particularly in cancerously transformed cells, while normal healthy cells are typically nonresponsive. We have previously demonstrated that pluripotent human embryonic stem cells (hESC) are also refractory to TRAIL, even though they express all canonical components of the death receptor-induced apoptosis pathway. In this study, we have examined a capacity of DNA damage to provoke sensitivity of hESC to TRAIL. The extent of DNA damage, behavior of molecules involved in apoptosis, and response of hESC to TRAIL were investigated. The exposure of hESC to 1 mu M and 2 mu M concentrations of cisplatin have led to the formation of 53BP1 and gamma H2AX foci, indicating the presence of double-strand breaks in DNA, without affecting the expression of proteins contributing to mitochondrial membrane integrity. Interestingly, cisplatin upregulated critical components of the extrinsic apoptotic pathway-initiator caspase 8, effector caspase 3, and the cell death receptors. The observed increase of expression of the extrinsic apoptotic pathway components was sufficient to sensitize hESC to TRAIL-induced apoptosis; immense cell dying accompanied by enhanced PARP cleavage, processing of caspase 8, and full activation of caspase 3 were all observed after the treatment combining cisplatin and TRAIL. Finally, we have demonstrated the central role of caspase 8 in this process, since its downregulation abrogated the sensitizing effect of cisplatin.

Links

NV16-31501A, research and development project

Name: Tkáňové inženýrství epitelů: Buňky a protokoly pro regenerativní medicínu

Citovat

PEŠKOVÁ, Lucie, Vladimír VINARSKÝ, Tomáš BÁRTA and Aleš HAMPL. Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin. Stem Cells International. London: HINDAWI LTD, 2019, vol. 2019, JAN 21 2019, p. 1-11. ISSN 1687-966X. Available from: https://dx.doi.org/10.1155/2019/4279481.

@article{1550497,
   author = {Pešková, Lucie and Vinarský, Vladimír and Bárta, Tomáš and Hampl, Aleš},
   article_location = {London},
   article_number = {JAN 21 2019},
   doi = {http://dx.doi.org/10.1155/2019/4279481},
   keywords = {APOPTOSIS-INDUCING LIGAND; ANTITUMOR-ACTIVITY; CARCINOMA CELLS; DNA; DEATH; DIFFERENTIATION; COMBINATION; ACTIVATION; CASPASE-10; RECEPTORS},
   language = {eng},
   issn = {1687-966X},
   journal = {Stem Cells International},
   title = {Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin},
   url = {https://www.hindawi.com/journals/sci/2019/4279481/},
   volume = {2019},
   year = {2019}
}

TY  - JOUR
ID  - 1550497
AU  - Pešková, Lucie - Vinarský, Vladimír - Bárta, Tomáš - Hampl, Aleš
PY  - 2019
TI  - Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin
JF  - Stem Cells International
VL  - 2019
IS  - JAN 21 2019
SP  - 1-11
EP  - 1-11
PB  - HINDAWI LTD
SN  - 1687966X
KW  - APOPTOSIS-INDUCING LIGAND
KW  - ANTITUMOR-ACTIVITY
KW  - CARCINOMA CELLS
KW  - DNA
KW  - DEATH
KW  - DIFFERENTIATION
KW  - COMBINATION
KW  - ACTIVATION
KW  - CASPASE-10
KW  - RECEPTORS
UR  - https://www.hindawi.com/journals/sci/2019/4279481/
L2  - https://www.hindawi.com/journals/sci/2019/4279481/
N2  - Tumor necrosis factor-related apoptosis-inducing ligand-TRAIL-is a protein operating as a ligand capable of inducing apoptosis particularly in cancerously transformed cells, while normal healthy cells are typically nonresponsive. We have previously demonstrated that pluripotent human embryonic stem cells (hESC) are also refractory to TRAIL, even though they express all canonical components of the death receptor-induced apoptosis pathway. In this study, we have examined a capacity of DNA damage to provoke sensitivity of hESC to TRAIL. The extent of DNA damage, behavior of molecules involved in apoptosis, and response of hESC to TRAIL were investigated. The exposure of hESC to 1 mu M and 2 mu M concentrations of cisplatin have led to the formation of 53BP1 and gamma H2AX foci, indicating the presence of double-strand breaks in DNA, without affecting the expression of proteins contributing to mitochondrial membrane integrity. Interestingly, cisplatin upregulated critical components of the extrinsic apoptotic pathway-initiator caspase 8, effector caspase 3, and the cell death receptors. The observed increase of expression of the extrinsic apoptotic pathway components was sufficient to sensitize hESC to TRAIL-induced apoptosis; immense cell dying accompanied by enhanced PARP cleavage, processing of caspase 8, and full activation of caspase 3 were all observed after the treatment combining cisplatin and TRAIL. Finally, we have demonstrated the central role of caspase 8 in this process, since its downregulation abrogated the sensitizing effect of cisplatin.
ER  -

PEŠKOVÁ, Lucie, Vladimír VINARSKÝ, Tomáš BÁRTA and Aleš HAMPL. Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin. \textit{Stem Cells International}. London: HINDAWI LTD, 2019, vol.~2019, JAN 21 2019, p.~1-11. ISSN~1687-966X. Available from: https://dx.doi.org/10.1155/2019/4279481.

Detailed Information on Publication Record