1-1-diphenyl-2-picrylhydrazyl and phenethyl-isothiocyanate

Isothiocyanates are plant-derived compounds that may be beneficial in the prevention of certain chronic diseases. Yet, by stimulating the production of reactive oxygen species (ROS), isothiocyanates can be genotoxic. Whether antioxidants influence isothiocyanate-induced genotoxicity is unclear, but this situation was clarified appreciably herein. In HCT116 cells, phenethyl isothiocyanate (PEITC) increased ROS production, which was inhibited by N-acetylcysteine (NAC) and deferoxamine (DFO) but not by ascorbic acid (ASC) and trolox (TRX) that were found to be more potent radical scavengers. Surprisingly, ASC and TRX each intensified the DNA damage that was caused by PEITC, but neither ASC nor TRX by themselves caused any DNA damage. In contrast, NAC and DFO each not only attenuated PEITC-induced DNA damage but also attenuated the antioxidant-intensified, PEITC-induced DNA damage. To determine if the DNA damage could be related to possible changes in the major antioxidant defence system, glutathione (GSH) was investigated. PEITC lowered GSH levels, which was prevented by NAC, whereas ASC, TRX and DFO neither inhibited nor enhanced the GSH-lowering effect of PEITC. The GSH synthesis inhibitor, buthionine sulphoxime, intensified PEITC-induced DNA damage, although by itself buthionine sulphoxime did not directly cause DNA damage. The principal findings suggest that ASC and TRX make PEITC more genotoxic, which might be exploited in killing cancer cells as one approach in killing cancer cells is to extensively damage their DNA so as to initiate apoptosis.

Topics: Apoptosis; Ascorbic Acid; Biphenyl Compounds; Chromans; DNA Damage; Drug Evaluation, Preclinical; Free Radical Scavengers; Glutathione; HCT116 Cells; HT29 Cells; Humans; Isothiocyanates; Mutagens; Picrates; Reactive Oxygen Species

In this study, the protective effects of Brussels sprouts extract and its major constituents against oxidative stress-induced damages were investigated in rat pheochromocytoma cells and Institute of Cancer Research mice. The major constituents of Brussels sprouts (3,4',5,7-tetrahydroxyflavone (kaempferol), indole-3-carbinol, and phenethyl isothiocyanate) were selectively tested. Of these, the flavonoid compound, kaempferol exhibited the highest potency in radical scavenging activity (1,1-diphenyl-2-picryl hydrazyl assay and oxygen radical absorbance capacity assay) and was most protective against oxidative stress in neuronal cell assays (measurement of intracellular oxidative stress levels and cell viability). In mice, after 4 weeks of kaempferol administration, significant protection against amyloid beta (Aβ) peptide-induced neurotoxicity was also observed, as assessed through the passive avoidance test. Taken together, the results suggest that Brussels sprouts could be protective against Aβ-induced neurotoxicity, possibly due to the antioxidative capacity of its major constituent, kaempferol.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Biphenyl Compounds; Brain; Brassica; Cell Survival; Indoles; Isothiocyanates; Kaempferols; Mice; Mice, Inbred ICR; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; PC12 Cells; Picrates; Plant Extracts; Rats