Antiapoptotic effects of dietary antioxidants towards N-nitrosopiperidine and N-nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells.
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.
García
Almudena
A
Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Universidad Complutense de Madrid, Spain.
Morales
Paloma
P
Arranz
Nuria
N
Delgado
Ma Eugenia
ME
Rafter
Joseph
J
Haza
Ana I
AI
D000498:Allyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D019587:Dietary Supplements; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009602:Nitrosamines / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000498:Allyl Compounds; D000975:Antioxidants; D004220:Disulfides; D009602:Nitrosamines; D017382:Reactive Oxygen Species; C028009:diallyl disulfide; C002743:N-nitrosopiperidine; C012279:dibutylnitrosamine; C041288:n-propyl disulfide; D001205:Ascorbic Acid