Intracellular accumulation of structurally varied isothiocyanates correlates with inhibition of nitric oxide production in proinflammatory stimuli-activated tumorigenic macrophage-like cells.
Bioorg Med Chem
; 22(1): 440-6, 2014 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-24268367
ABSTRACT
In the present study, we analyzed the intracellular accumulation of 6-(methylsulfinyl)hexyl isothiocyanate (6MITC) and its analogs in proinflammatory stimuli-activated J774.1 cells to predict the biological potencies of the ITCs. Our present analyses exhibited that the intracellular accumulation was in the order of 6MITC>2b>2e≈2c>2g>2d>2f>2h. Investigation of reactivity of the ITCs with glutathione (GSH) in the tumor cells revealed partial inhibition of GSH by the ITCs. Furthermore, the inhibition of nitric oxide (NO) production in the tumor cells was ascribed to the intracellularly accumulated ITCs. The NO suppression was correlated with the inhibition of tumor cell growth. Our present results suggest that the intracellular accumulation of the ITCs can be used to predict their biological potencies, such as inhibition of NO production that was correlated with suppression of tumor cell growth. To the best of our knowledge, this is the first report to predict the biological potency of 6MITC and its analogs with their intracellular accumulation.
Palavras-chave
(±)-N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexene-1-yl]-3-pyridine carboxamide; 6-(Methylsulfinyl)hexyl isothiocyanate; 6-(methylsulfinyl)hexyl isothiocyanate; 6MITC; ABC; ATP-binding cassette; GSH; Glutathione; IC(50); IFN-γ; IRF-1; ITC; K(obs); LBS; LPS; MDR; NF-κB; NO; NOR4; Nitric oxide; P-glycoprotein; P-gp; PSA; Pseudo-first order reaction rate constant; S-nitroso-N-acetyl-dl-penicillamine; SNAP; glutathione; half-maximal inhibitory concentration; iNOS; inducible NO synthase; interferon regulatory factor-1; interferon-gamma; isothiocyanate; ligand-binding site; lipopolysaccharide; logP; logarithm of partition coefficient between 1-octanol and aqueous phases; multidrug resistance; nitric oxide; nuclear factor-κB; polar surface area
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Isotiocianatos
/
Óxido Nítrico
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article