title: Magnolol-induced apoptosis is mediated via the intrinsic pathway with release of AIF from mitochondria in U937 cells.
abstract: Magnolol has been reported to have an inhibitory effect on tumor invasion in vitro and in vivo. In this study, we found that treatment with 30 microM magnolol exhibited growth inhibition partly by inducing apoptosis in cultured human leukemia U937 cells and that the apoptosis was induced via the sequential ordering of molecular events; 1) a transient decrease of phosphorylated extracelluar signal-requlated kinase (ERK), 2) translocation of apoptosis inducing factor (AIF) from mitochondria to cytosol concurrent with a decreased membrane potential, and 3) downregulation of bcl-2 protein. Pretreatment of the cells with a pan-caspase inhibitor Z-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) did not prevent the apoptosis induced by magnolol. These findings indicated that the above-mentioned sequence of intracellular signaling events led to apoptosis in magnolol-treated U937 cells, which was caspase-independent.
authors.affiliation: Gifu International Institute of Biotechnology, Kakamigahara, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ikai
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohguchi
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sakai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020298:U937 Cells
chemical_list: D051033:Apoptosis Inducing Factor; D001713:Biphenyl Compounds; D017705:Lignans; C005498:magnolol; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases