Antiapoptotic effects of dietary antioxidants towards N-nitrosopiperidine and N-nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells.

Abstract

The aim of this work was to determine the effect of vitamin C, diallyl disulfide (DADS) and dipropyl disulfide (DPDS) towards N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA)-induced apoptosis in human leukemia (HL-60) and hepatoma (HepG2) cell lines using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. None of the vitamin C (5-50 microm), DADS and DPDS (1-5 microm) concentrations selected induced a significant percentage of apoptosis. In simultaneous treatments, vitamin C, DADS and DPDS reduced the apoptosis induced by NPIP and NDBA in HL-60 and HepG2 cells (around 70% of reduction). We also investigated its scavenging activities towards reactive oxygen species (ROS) produced by NPIP and NDBA using 2',7'-dichlorodihydrofluorescein diacetate in both cell lines. ROS production induced by both N-nitrosamine was reduced to control levels by vitamin C (5-50 microm) in a dose-dependent manner. However, DADS (5 microm) increased ROS levels induced by NPIP and NDBA in HL-60 (40 and 20% increase, respectively) and HepG2 cells (18% increase), whereas DPDS was more efficient scavenger of ROS at the lowest concentration (1 microm) in both HL-60 (52 and 25% reduction, respectively) and HepG2 cells (24% reduction). The data demonstrated that the scavenging ability of vitamin C and DPDS could contribute to inhibition of the NPIP- and NDBA-induced apoptosis. However, more than one mechanism, such as inhibition of phase I and/or induction of phase II enzymes, could be implicated in the protective effect of dietary antioxidants towards NPIP- and NDBA-induced apoptosis in HL-60 and HepG2 cells.

• Authors: Almudena García, Paloma Morales, Nuria Arranz, Ma Eugenia Delgado, Joseph Rafter, Ana I Haza
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) Vol. 29 Issue 5 Pg. 403-13 (Jul 2009) ISSN: 1099-1263 [Electronic] England
• PMID: 19301245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 John Wiley & Sons, Ltd.

Chemical References

• Allyl Compounds
• Antioxidants
• Disulfides
• Nitrosamines
• Reactive Oxygen Species
• diallyl disulfide
• N-nitrosopiperidine
• dibutylnitrosamine
• n-propyl disulfide
• Ascorbic Acid

Topics

• Allyl Compounds (administration & dosage, pharmacology)
• Antioxidants (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Ascorbic Acid (administration & dosage, pharmacology)
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Culture Techniques
• Dietary Supplements
• Disulfides (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• HL-60 Cells
• Humans
• In Situ Nick-End Labeling
• Leukemia, Promyelocytic, Acute (metabolism, pathology)
• Liver Neoplasms (metabolism, pathology)
• Nitrosamines (toxicity)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)