Pt(II) complex containing the 1R,2R enantiomer of trans-1,2-diamino-4-cyclohexene ligand effectively and selectively inhibits the viability of aggressive pancreatic adenocarcinoma cells and alters their lipid metabolism
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00558795" target="_blank" >RIV/68081707:_____/22:00558795 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2022/QI/D2QI00778A" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2022/QI/D2QI00778A</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d2qi00778a" target="_blank" >10.1039/d2qi00778a</a>
Alternative languages
Result language
angličtina
Original language name
Pt(II) complex containing the 1R,2R enantiomer of trans-1,2-diamino-4-cyclohexene ligand effectively and selectively inhibits the viability of aggressive pancreatic adenocarcinoma cells and alters their lipid metabolism
Original language description
Here, we investigated the mechanism of antiproliferative action in cancer cells of new compounds structurally derived from oxaliplatin, namely a pair of enantiomers [Pt(OXA)(1R,2R-DACHEX)] (1) and [Pt(OXA)(1S,2S-DACHEX)] (2) (OXA = oxalate, DACHEX = trans-1,2-diamino-4-cyclohexene). While oxaliplatin is used almost exclusively to treat colorectal and other gastrointestinal cancers, new complex 1 shows instead high potency in malignant pancreatic adenocarcinoma PSN1 cells including superior selectivity for pancreatic cancer over noncancerous cells. Utilizing a multi-platform biochemical approach to study the unique features of the mechanism of action of this new platinum-based drug, we show that 1 has a much greater ability to penetrate pancreatic tumors than its S,S enantiomer 2 and oxaliplatin, and to be transported into cells as bound to plasma proteins. Additionally, the mechanism of action of 1 and, to a lesser extent, oxaliplatin in pancreatic cancer cells involves alterations of the lipogenesis pathway, namely inhibition of de novo lipid synthesis, acting by a new mechanism not yet considered for anticancer action of clinically used antitumor platinum drugs. These data highlight the functional diversity of platinum anticancer compounds and the potential benefits of finding new anticancer drugs applying a mechanism-based rationale.
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
10601 - Cell biology
Result continuities
Project
<a href="/en/project/LTAUSA18009" target="_blank" >LTAUSA18009: The next generation of platinum anticancer drugs. Molecular and cellular mechanisms of action</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganic Chemistry Frontiers
ISSN
2052-1553
e-ISSN
2052-1553
Volume of the periodical
9
Issue of the periodical within the volume
13
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
3295-3305
UT code for WoS article
000804232100001
EID of the result in the Scopus database
2-s2.0-85131733537