Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells.
10.3346/jkms.2011.26.11.1474
- Author:
Yoon Jin LEE
1
;
Sang Han LEE
Author Information
1. Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, Korea. m1037624@sch.ac.kr
- Publication Type:Original Article
- Keywords:
Sulforaphane;
Nrf2;
Heme Oxygenase-1;
Reactive Oxygen Species;
BEAS-2B Cells;
Oxidative Stress
- MeSH:
Acetylcysteine/pharmacology;
Anticarcinogenic Agents/pharmacology;
Antioxidants/*pharmacology;
Bronchi/cytology/*drug effects/metabolism;
Cell Line;
Cell Proliferation/*drug effects;
Epithelial Cells/drug effects/metabolism;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Free Radical Scavengers/pharmacology;
Heme Oxygenase-1/biosynthesis;
Humans;
NF-E2-Related Factor 2/biosynthesis/genetics;
Oxidative Stress/drug effects;
Proto-Oncogene Proteins c-akt/metabolism;
RNA Interference;
RNA, Small Interfering;
Reactive Oxygen Species/*metabolism;
Respiratory Mucosa/cytology/*drug effects/metabolism;
Signal Transduction/drug effects;
Thiocyanates/*pharmacology
- From:Journal of Korean Medical Science
2011;26(11):1474-1482
- CountryRepublic of Korea
- Language:English
-
Abstract:
Sulforaphane (SFN) is a naturally occurring compound which is known to induce the phase II antioxidant genes via Nrf2 activation, although the underlying mechanism has not been fully elucidated. In this study, we investigated Nrf2 induction in response to SFN in human bronchial epithelial BEAS-2B cells and determined the signaling pathways involved in this process. SFN treatment reduced cell viability. Prior to cell death, intracellular reactive oxygen species (ROS) were generated at a high rate within a minute of commencing SFN treatment. Pretreatment with antioxidant N-acetylcysteine (NAC) blocked SFN-induced decrease in cell growth. Erk1/2 was activated within 30 min of SFN addition, whereas Akt phosphorylation did not significantly change until the first 8 hr after SFN treatment but then became substantially low until 48 hr. Inhibition of Erk1/2 phosphorylation attenuated SFN-induced loss of cell viability. Nrf2 protein levels in both nuclear and whole cell lysates were increased by SFN treatment, which was dependent on ROS production. Knockdown of Nrf2 with siRNA attenuated SFN-induced heme oxygenase-1 (HO-1) up-regulation. Induction of the Nrf2/HO-1 after SFN treatment was potently suppressed by pretreatment with NAC. Overall, our results indicate that SFN mediates antioxidative and antiproliferative responses by generating ROS in BEAS-2B cells.
