Anticancer dinuclear Ir(III) complex activates Nrf2 and interferes with NAD(H) in cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73625679" target="_blank" >RIV/61989592:15310/25:73625679 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0162013424002289" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0162013424002289</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jinorgbio.2024.112704" target="_blank" >10.1016/j.jinorgbio.2024.112704</a>
Alternative languages
Result language
angličtina
Original language name
Anticancer dinuclear Ir(III) complex activates Nrf2 and interferes with NAD(H) in cancer cells
Original language description
Dinuclear complex [Ir2(μ-L1)(η5-Cp*)2Cl2](PF6)2 (1) exhibits low micromolar cytotoxic activity in vitro in various human cancer cells (GI50 = 1.7–3.0 μM) and outperformed its mononuclear analogue [Ir(η5-Cp*)Cl(L2)]PF6 (2; GI50 > 40.0 μM); Cp* = pentamethylcyclopentadienyl, L1 = 4-chloro-2,6-bis[5-(pyridin-2-yl)-1,3,4-thiadiazol-2-yl]pyridine, L2 = 5-(pyridin-2-yl)-1,3,4-thiadiazol-2-amine. Compound 1 upregulated the Keap1/Nrf2 oxidative stress-protective pathway in the treated MV4–11 acute myeloid leukemia cells. In connection with the redox-mediated mode of action of 1, its NADH-oxidizing activity was detected in solution (1H NMR), while NAD+ remained intact (with formate as a hydride source). Surprisingly, only negligible NADH oxidation was detected in the presence of the reduced glutathione and ascorbate. Following the results of in-solution experiments, NAD(H) concentration was assessed in 1-treated MV4–11 cancer cells. Besides the intracellular NADH oxidation in the presence of 1, the induced oxidative stress also led to a decrease of NAD+, resulting in depletion of both NAD+/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.
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/NU22-08-00236" target="_blank" >NU22-08-00236: Pre-clinical study of non-platinum metalodrugs for lung cancer therapy</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
JOURNAL OF INORGANIC BIOCHEMISTRY
ISSN
0162-0134
e-ISSN
1873-3344
Volume of the periodical
262
Issue of the periodical within the volume
JAN
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
"12704-1"-"112704-9"
UT code for WoS article
001334089500001
EID of the result in the Scopus database
2-s2.0-85203236951