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The isothiocyanate erucin induces reactive oxygen species and a transient decrease in glutathione in human liver cancer cells
Author(s) -
Eberhardt Marian V,
Jeffery Elizabeth H
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a155-b
Subject(s) - glutathione , oxidative stress , reactive oxygen species , isothiocyanate , sulforaphane , antioxidant , chemistry , intracellular , biochemistry , cancer cell , cruciferous vegetables , enzyme , biology , cancer , genetics
Both epidemiological and animal studies have shown isothiocyanates from cruciferous vegetables to be potent anticancer agents. Isothiocyanates are thought to provide chemoproctection by inducing detoxification and enhanced antioxidant power (induced antioxidant enzymes and glutathione synthesis). However, upregulation of proteins takes several hours and other studies have shown that acutely, isothiocyanates may induce cellular oxidative stress. The objective of this study was to determine the acute effect of erucin, the reduced analog of sulforaphane, on oxidative stress in human liver cancer (HepG2) cells. Generation of intracellular oxidative stress was measured by flow cytometry using the fluorescent marker 2′,7‐dichlorofluorescin diacetate. Glutathione levels were determined using the fluorescent probe o‐phthaladehyde. Treatment of HepG2 cells with erucin resulted in a dose‐dependent increase in generation of intracellular reactive oxygen species (ROS). Erucin increased ROS by 1.6, 1.8, and 2.6‐fold over control at concentrations of 2.5, 20, and 40μM. Erucin (20μM) caused depletion of cellular glutathione levels in HepG2 cells at 1, 3, and 6h, with recovery by 24h. These data suggest that the initial effect of the isothiocyanate erucin may be oxidative rather than antioxidative, and that it may be this initial oxidative step that is responsible for triggering antioxidant response element (ARE)‐related signal transduction. Supported by USDA/IFAFS award 00‐04766.