J Korean Med Sci.  2011 Nov;26(11):1474-1482. 10.3346/jkms.2011.26.11.1474.

Sulforaphane Induces Antioxidative and Antiproliferative Responses by Generating Reactive Oxygen Species in Human Bronchial Epithelial BEAS-2B Cells

• Lee YJ
• Lee SH

• KMID: 1123448
• DOI: http://doi.org/10.3346/jkms.2011.26.11.1474

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.

Keyword

Sulforaphane; Nrf2; Heme Oxygenase-1; Reactive Oxygen Species; BEAS-2B Cells; Oxidative Stress

MeSH Terms

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