An Endoplasmic Reticulum Specific Pro-amplifier of Reactive Oxygen Species in Cancer Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F21%3A00550039" target="_blank" >RIV/61389030:_____/21:00550039 - isvavai.cz</a>
Result on the web
<a href="http://doi.org/10.1002/anie.202100054" target="_blank" >http://doi.org/10.1002/anie.202100054</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/anie.202100054" target="_blank" >10.1002/anie.202100054</a>
Alternative languages
Result language
angličtina
Original language name
An Endoplasmic Reticulum Specific Pro-amplifier of Reactive Oxygen Species in Cancer Cells
Original language description
The folding and export of proteins and hydrolysis of unfolded proteins are disbalanced in the endoplasmic reticulum (ER) of cancer cells, leading to so-called ER stress. Agents further augmenting this effect are used as anticancer drugs including clinically approved proteasome inhibitors bortezomib and carfilzomib. However, these drugs can affect normal cells, which also rely strongly on ER functions, leading, for example, to accumulation of reactive oxygen species (ROS). To address this problem, we have developed ER-targeted prodrugs activated only in cancer cells in the presence of elevated ROS amounts. These compounds are conjugates of cholic acid with N-alkylaminoferrocene-based prodrugs. We confirmed their accumulation in the ER of cancer cells, their anticancer efficacy, and cancer cell specificity. These prodrugs induce ER stress, attenuate mitochondrial membrane potential, and generate mitochondrial ROS leading to cell death via necrosis. We also demonstrated that the new prodrugs are activated in vivo in Nemeth-Kellner lymphoma (NK/Ly) murine model.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10601 - Cell biology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Angewandte Chemie - International Edition
ISSN
1433-7851
e-ISSN
1521-3773
Volume of the periodical
60
Issue of the periodical within the volume
20
Country of publishing house
DE - GERMANY
Number of pages
5
Pages from-to
11158-11162
UT code for WoS article
000637988500001
EID of the result in the Scopus database
2-s2.0-85104053100