title: Protuboxepin A, a marine fungal metabolite, inducing metaphase arrest and chromosomal misalignment in tumor cells.
abstract: Previously we reported the identification of a new oxepin-containing diketopiperazine-type marine fungal metabolite, named protuboxepin A which showed antiproliferative activity in several cancer cell lines. In this study we elucidated the mechanism by which protuboxepin A induces cancer cell growth inhibition. Here we report that protuboxepin A induced round-up morphology, M phase arrest, and an increase in the subG(1) population in tumor cells in a dose dependent manner. Our investigations revealed that protuboxepin A directly binds to α,β-tubulin and stabilizes tubulin polymerization thus disrupting microtubule dynamics. This disruption leads to chromosome misalignment and metaphase arrest which induces apoptosis in cancer. Overall, we identified protuboxepin A as a microtubule-stabilizing agent which has a distinctly different chemical structure from previously reported microtubule inhibitors. These results indicate that protuboxepin A has a potential of being a new and effective anti-cancer drug.
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea; Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Asami
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Nak-Kyun
authors.initials: NK
authors.lastname: Soung
authors.forename: Long
authors.initials: L
authors.lastname: He
authors.forename: Dong Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
authors.forename: Makoto
authors.initials: M
authors.lastname: Muroi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059001:Aquatic Organisms / Q000382:microbiology; D001230:Aspergillus / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D023902:Chromosome Pairing / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008677:Metaphase / Q000187:drug effects*; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010082:Oxepins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010082:Oxepins; D014404:Tubulin; C560174:protuboxepin A