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
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
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
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
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
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10601 - Cell biology
Návaznosti výsledku
Projekt
<a href="/cs/project/LTAUSA18009" target="_blank" >LTAUSA18009: Nová generace protinádorových léčiv na bázi platiny. Molekulární a buněčné mechanismy působení</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Inorganic Chemistry Frontiers
ISSN
2052-1553
e-ISSN
2052-1553
Svazek periodika
9
Číslo periodika v rámci svazku
13
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
11
Strana od-do
3295-3305
Kód UT WoS článku
000804232100001
EID výsledku v databázi Scopus
2-s2.0-85131733537