In vitro: In contrast to SK-N-BE(2) cells, co-treatment of IMR-32 cells with TTFA not only failed to stimulate formation of ROS produced by cisplatin, but rather suppressed it. This correlates with the attenuation of the caspase-3-like activity in response to combined treatment of IMR-32 cells with TTFA and cisplatin.
In vivo: TTFA-mediated inhibition of the ubiquinone-binding site of SDHD blocks electron transfer to ubiquinone and may lead to electron-slippage with the formation of superoxide radicals, thereby contributing to ROS production.
|Cell lines||NB cell lines|
|Preparation method||For the time lapse, cells were cultivated in the POC-R cell cultivation system at 37 °C and a humidified air/CO2 (5%) atmosphere. Cisplatin ± TTFA was bath-applied before the start of the time lapse and the fluorescence was recorded for 22 h.|
|Concentrations||75 μM, 100 μM|
|Incubation time||24 h|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy.
Kruspig B, et al. Biochim Biophys Acta. 2016 Aug;1863(8):2065-71. PMID: 27140478.
Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation
K Kluckova, et al. Cell Death Dis. 2015 May;6(5): e1749. PMID: 25950479.
|GJ103 sodium salt
GJ103 sodium salt is an active analog of the read-through compound GJ072.
Tubercidin (7-Deazaadenosine) is an adenosine analog, is an antibiotic obtained from Streptomyces tubercidicus.
ML-7 hydrochloride is a naphthalene sulphonamide derivative, potently inhibits MLCK (IC50=300 nM) and TRPC6 channel (IC50>10 μM).
Importazole is a small molecule inhibitor of the nuclear transport receptor importin-β.
Apoptozole is an inhibitor of the ATPase domain of Hsc70 and Hsp70, with Kds of 0.21 and 0.14 μM, respectively, and can induce apoptosis.
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