title: Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines.
abstract: The flavonoid, luteolin, has been shown to have anticancer activity in various cancer cells; however, the precise molecular mechanism of its action is not completely understood, and studies were conducted to find out how it induces apoptosis in breast cancer cells. Luteolin induced a reduction of viability in a dose- and time-dependent manner. The pro-apoptotic effect of luteolin was demonstrated by cell cycle measurement and Hoechst 3325 staining. Western blot analysis showed that luteolin activates ERK (extracellular-signal-regulated kinase) and p38. Pharmacological inhibition or knockdown of ERK and p38 protected against luteolin-induced cell death; however, the caspase-3-specific inhibitor had no effect. Immunocytochemical examination indicated that luteolin induced nuclear translocation of AIF (apoptosis-inducing factor), which was mediated by activation of ERK and p38. Transfection of a vector expressing the miRNA (microRNA) of AIF prevented luteolin-induced apoptosis. The data suggest that luteolin induces a caspase-dependent and -independent apoptosis involving AIF nuclear translocation mediated by activation of ERK and p38 in breast cancer cells.
authors.affiliation: Department of Physiology, College of Medicine, Pusan National University, Pusan 602739, Korea.
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Jae Suk
authors.initials: JS
authors.lastname: Woo
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Keun
authors.initials: YK
authors.lastname: Kim
authors.forename: Ki Hyung
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000235:genetics; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C494829:AIFM1 protein, human; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D035683:MicroRNAs; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D047311:Luteolin