title: 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 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.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan. Electronic address: hyamagu@meijo-u.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Kamiie
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kidachi
authors.affiliation: Department of Life Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara 727-0023, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Noshita
authors.affiliation: Laboratory of Food Chemistry, Department of Life Sciences, Junior College, Gifu Shotoku Gakuen University, 1-38 Nakauzura, Gifu 055-8288, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Umetsu
authors.affiliation: Department of Health Promotion Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, 1-1 Minamiosawa, Hachioji 192-0397, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fuke
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Aomori University, 2-3-1 Kobata, Aomori 030-0943, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ryoyama
mesh_terms: D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D017879:Isothiocyanates; C037152:isothiocyanic acid; D009569:Nitric Oxide
keywords: (±)-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