title: Apicularen A acetate induces cell death via AIF translocation and disrupts the microtubule network by down-regulating tubulin in HM7 human colon cancer cells.
abstract: Apicularen A is a novel antitumor agent and strongly induces death in tumor cells. In this study, we synthesized apicularen A acetate, an acetyl derivative of apicularen A, and investigated its antitumor effect and mechanism in HM7 colon cancer cells. Apicularen A acetate induced apoptotic cell death and caspase-3 activation; however, the pan-caspase inhibitor Z-VAD-fmk could not prevent this cell death. Apicularen A acetate induced the loss of mitochondrial membrane potential and the translocation of apoptosis-inducing factor (AIF) from mitochondria. In addition, apicularen A acetate significantly decreased tubulin mRNA and protein levels and induced disruption of microtubule networks. Taken together, these results indicate that the mechanism of apicularen A acetate involves caspase-independent apoptotic cell death and disruption of microtubule architecture.
authors.affiliation: Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Kang-Sik
authors.initials: KS
authors.lastname: Seo
authors.forename: Hoon
authors.initials: H
authors.lastname: Kim
authors.forename: Tae-Hwa
authors.initials: TH
authors.lastname: Hong
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Kyoung-Sub
authors.initials: KS
authors.lastname: Song
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Yun
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Park
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Jung
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Park
authors.forename: Gi Ryang
authors.initials: GR
authors.lastname: Kweon
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoon
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
authors.forename: Byung-Doo
authors.initials: BD
authors.lastname: Hwang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014404:Tubulin / Q000378:metabolism*
chemical_list: D051033:Apoptosis Inducing Factor; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014404:Tubulin; C117813:apicularen A