Triplex metallohelices have enantiomer-dependent mechanisms of action in colon cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00572385" target="_blank" >RIV/68081707:_____/23:00572385 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2023/dt/d3dt00948c" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2023/dt/d3dt00948c</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d3dt00948c" target="_blank" >10.1039/d3dt00948c</a>
Alternative languages
Result language
angličtina
Original language name
Triplex metallohelices have enantiomer-dependent mechanisms of action in colon cancer cells
Original language description
Self-assembled enantiomers of an asymmetric di-iron metallohelix differ in their antiproliferative activities against HCT116 colon cancer cells such that the compound with ?-helicity at the metals becomes more potent than the Delta compound with increasing exposure time. From concentration- and temperature-dependent Fe-57 isotopic labelling studies of cellular accumulation we postulate that while the more potent ? enantiomer undergoes carrier-mediated efflux, for Delta the process is principally equilibrative. Cell fractionation studies demonstrate that both enantiomers localise in a similar fashion, compound is observed mostly within the cytoskeleton and/or genomic DNA, with significant amounts also found in the nucleus and membrane, but with negligible concentration in the cytosol. Cell cycle analyses using flow cytometry reveal that the Delta enantiomer induces mild arrest in the G(1) phase, while ? causes a very large dose-dependent increase in the G(2)/M population at a concentration significantly below the relevant IC50. Correspondingly, G(2)-M checkpoint failure as a result of ?-metallohelix binding to DNA is shown to be feasible by linear dichroism studies, which indicate, in contrast to the Delta compound, a quite specific mode of binding, probably in the major groove. Further, spindle assembly checkpoint (SAC) failure, which could also be responsible for the observed G(2)/M arrest, is established as a feasible mechanism for the ? helix via drug combination (synergy) studies and the discovery of tubulin and actin inhibition. Here, while the ? compound stabilizes F-actin and induces a distinct change in tubulin architecture of HCT116 cells, Delta promotes depolymerization and more subtle changes in microtubule and actin networks.
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
10402 - Inorganic and nuclear chemistry
Result continuities
Project
<a href="/en/project/GA21-27514S" target="_blank" >GA21-27514S: Metal-based compounds for enhanced cancer immunotherapy</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Dalton Transactions
ISSN
1477-9226
e-ISSN
1477-9234
Volume of the periodical
52
Issue of the periodical within the volume
20
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
6656-6667
UT code for WoS article
000975765100001
EID of the result in the Scopus database
2-s2.0-85158816033