title: Alpinumisoflavone induces apoptosis and suppresses extracellular signal-regulated kinases/mitogen activated protein kinase and nuclear factor-κB pathways in lung tumor cells.
abstract: The extracellular signal-regulated kinases/mitogen activated protein kinase (ERK/MAPK) and nuclear factor-κB (NF-κB) pathways are critical for cell survival and proliferation. Alpinumisoflavone (AIF), isolated from the African medicinal plant Erythrina lysistemon, is a member of the isoflavone group. In this report, we demonstrated that AIF treatment induces cell death of human lung tumor cells. Incubation of lung tumor cells with AIF 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 AIF significantly deregulated both the ERK/MAPK and NF-κB pathways. Western blot analysis with antibodies to MAP/ERK kinase (MEK) and ERK showed that AIF dephosphorylates both MEK and ERK. Alpinumisoflavone also repressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells by inhibiting NF-κB-dependent transcription. Therefore, the cell death induced by AIF may be via repressing both the ERK/MAPK and NF-κB pathways.
authors.affiliation: Division of Biological Science and Technology, Yonsei University.
authors.forename: Sim
authors.initials: S
authors.lastname: Namkoong
authors.forename: Tack-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
authors.forename: Keon-Wook
authors.initials: KW
authors.lastname: Kang
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Oh
authors.forename: Junsoo
authors.initials: J
authors.lastname: Park
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004895:Erythrina / Q000737:chemistry*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; C000154:alpinumisoflavone; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases