Premium
N‐Nitrosopiperidine and N‐Nitrosodibutylamine induce apoptosis in HepG2 cells via the caspase dependent pathway
Author(s) -
García Almudena,
Morales Paloma,
Rafter Joseph,
Haza Ana I.
Publication year - 2009
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2009.08.015
Subject(s) - apoptosis , reactive oxygen species , caspase , programmed cell death , microbiology and biotechnology , intrinsic apoptosis , chemistry , cell culture , cell , biology , cancer research , biochemistry , genetics
The human hepatoma cell line (HepG2) exhibited a dose and time‐dependent apoptotic response following treatment with N‐Nitrosopiperidine (NPIP) and N‐Nitrosodibutylamine (NDBA), two recognized human carcinogens. Our results showed a significant apoptotic cell death (95%) after 24 h treatment with NDBA (3.5 mM), whereas it was necessary to use high doses of NPIP (45 mM) to obtain a similar percentage of apoptotic cells (86%). In addition, both extrinsic (caspase‐8) and intrinsic pathway (caspase‐9) could be implicated in the N‐Nitrosamines‐induced apoptosis. This study also addresses the role of reactive oxygen species (ROS) as intermediates for apoptosis signaling. A significant increase in ROS levels was observed after NPIP treatment, whereas NDBA did not induce ROS. However, N‐acetylcysteine (NAC) did not block NPIP‐induced apoptosis. All these findings suggest that NPIP and NDBA induce apoptosis in HepG2 cells via a pathway that involves caspases but not ROS.