Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: Implication for prevention against inflammation-related carcinogenesis

Noriyuki Miyoshi, Satoko Takabayashi, Toshihiko Osawa, Yoshimasa Nakamura

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Inhibitors of excessive superoxide (O2-) generation have been indicated to be more effective antioxidants than radical scavengers because O2- anion is one of the precursors of several types of reactive oxygen species (ROS). We demonstrated here that benzyl isothiocyanate (BITC) is a potent inhibitor of leukocytic NADPH oxidase generating a great amount of O2- in oxidative burst. The exposure of BITC to the differentiated HL-60 cells resulted in the inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced O2 - generation, while the methylthiocarbamate analog of BITC, hardly reactive with thiols including glutathione and protein sulfhydryl, did not show any effect. Pre-treatment of the cells with diethyl maleate significantly potentiated the BITC-induced inhibition, while pre-treatment with N-acetyl-cysteine counteracted it. These results led us to assume that a plausible intracellular target molecule(s) having a reactive sulfhydryl moiety might be regulated by the covalent attachment with BITC. In spite of no ability to affect the translocation of protein kinase C β to the membrane, BITC probably modifies the electron transport system of cytochrome b558, consistent with the observation that BITC inhibited the substrate utilization. Pre-treatments of mouse skin with BITC significantly attenuated the TPA-enhanced hydrogen peroxide level, suggesting that BITC indeed acts as an inhibitor Of O2- generation in mouse skin. A histological study also demonstrated that BITC inhibited TPA-induced leukocyte infiltration in the dermis. Because we have found several O2- generation inhibitors to be effective chemopreventors against mouse skin carcinogenesis, the modifying effect of the topical application of BITC on TPA-induced mouse skin tumor promotion was investigated. We demonstrated for the first time that the pre-treatment with BITC 40 min prior to each TPA treatment significantly inhibited the number of papillomas per mouse. In conclusion, the results from this study provided biological evidence that BITC has a potential to prevent inflammation-related carcinogenesis including skin cancer.

Original languageEnglish
Pages (from-to)567-575
Number of pages9
JournalCarcinogenesis
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

Fingerprint

Superoxides
Carcinogenesis
Leukocytes
Inflammation
Tetradecanoylphorbol Acetate
Skin
diethyl maleate
benzyl isothiocyanate
Respiratory Burst
NADPH Oxidase
HL-60 Cells
Papilloma
Skin Neoplasms
Dermis
Electron Transport
Sulfhydryl Compounds
Protein Kinase C
Hydrogen Peroxide
Anions
Glutathione

ASJC Scopus subject areas

  • Cancer Research

Cite this

Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes : Implication for prevention against inflammation-related carcinogenesis. / Miyoshi, Noriyuki; Takabayashi, Satoko; Osawa, Toshihiko; Nakamura, Yoshimasa.

In: Carcinogenesis, Vol. 25, No. 4, 04.2004, p. 567-575.

Research output: Contribution to journalArticle

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