title: Vaticanol C-induced cell death is associated with inhibition of pro-survival signaling in HL60 human leukemia cell line.
abstract: Recently, we found that vaticanol C (a resveratrol tetramer), which was isolated from stem bark of Dipterocarpaceae, exhibited growth suppression and induction of apoptosis via the loss of mitochondrial membrane potential and consequent caspases activation. The detailed mechanisms are not clearly understood. We decided to attempt to gain further insight into the mechanisms underlying vaticanol C-induced apoptosis in HL-60 cells. Treatment of HL-60 cells with vaticanol C was found to cause a marked decrease in the level of phosphorylated extracellular signal-regulated kinase (ERK) concurrent with inhibited phosphorylation of its upstream kinase mitogen-activates protein kinase kinase (MEK). Moreover, exposure to vaticanol C led to a significant reduction in the level of phosphorylated Akt. Thus, vaticanol C induced inhibition of both ERK and Akt phosphorylation, resulting in reduced phosphorylation of Bad. These results suggest that vaticanol C might induce apoptosis via a mechanism involving activation of Bad through disruption of pro-survival signaling pathways.
authors.affiliation: Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan. kohguchi@giib.or.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohguchi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ito
authors.forename: Munekazu
authors.initials: M
authors.lastname: Iinuma
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004791:Enzyme Inhibitors; D018922:HL-60 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D013267:Stilbenes; C459559:vaticanol C