Intracellular accumulation of structurally varied isothiocyanates correlates with inhibition of nitric oxide production in proinflammatory stimuli-activated tumorigenic macrophage-like cells.

Abstract In the present study, we analyzed the intracellularaccumulation of 6-(methylsulfinyl)hexyl isothiocyanate(6MITC) and its analogs in proinflammatory stimuli-activated J774.1 cells to predict the biological potenciesof the ITCs. Our present analyses exhibited that the intracellularaccumulation 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 intracellularaccumulation 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 potencyof 6MITC and its analogs with their intracellularaccumulation.