Alpinumisoflavone Induces Apoptosis and Suppresses Extracellular Signal-Regulated Kinases/Mitogen Activated Protein Kinase and Nuclear Factor-kappa B Pathways in Lung Tumor Cells

摘要

The extracellular signal-regulated kinases/mitogen activated protein kinase (ERK/MAPK) and nuclear factor-kappa B (NF-kappa B) pathways are critical for cell survival and proliferation. Alpinumisoflavone (AlF), isolated from the African medicinal plant Erythrina lysistemon, is a member of the isoflavone group. In this report, we demonstrated that AlF treatment induces cell death of human lung tumor cells. Incubation of lung tumor cells with AlF increased the sub-G1 population and caspase 3/7 activity, suggesting that the cell death is caused by apoptosis. To identify the signaling pathway involved in the tumor cell death, we examined the modulation of transcriptional activity using various reporter constructs and found that AlF significantly deregulated both the ERK/MAPK and NF-kappa B pathways. Western blot analysis with antibodies to MAP/ERK kinase (MEK) and ERK showed that AlF dephosphorylates both MEK and ERK. Alpinumisoflavone also repressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells by inhibiting NF-kappa B-dependent transcription. Therefore, the cell death induced by AlF may be via repressing both the ERK/MAPK and NF-kappa B pathways.