title: Latrunculin a has a strong anticancer effect in a peritoneal dissemination model of human gastric cancer in mice.
abstract: Peritoneal dissemination of gastric cancer is a refractory disease. This paper focuses on the efficacy of actin-binding marine macrolide latrunculin A, which quickly inhibits actin polymerization and disrupts the function of the actin cytoskeleton. The effects of latrunculin A on cell viability in vitro were evaluated by treatment of MKN45 or NUGC-4 cell cultures. An in vitro viability assay demonstrated an anticancer effect of latrunculin A in a dose-dependent manner. Latrunculin A induced acute cell injury and programmed cell death through activating the caspase-3/7 pathway. In vivo, MKN45 or NUGC-4 cells were intraperitoneally inoculated into nude mice, as a model of peritoneal dissemination. Intraperitoneal (i.p.) injection of latrunculin A significantly improved survival rate in mice without any major side-effects. Data indicated that latrunculin A has strong anticancer effects, and it may be a new candidate i.p. drug against peritoneal dissemination of gastric cancer in humans.
authors.affiliation: Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Konishi
authors.forename: Shojiro
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Ochiai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ikoma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubota
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.forename: Chouhei
authors.initials: C
authors.lastname: Sakakura
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Sonoyama
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kokuba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsui
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D018279:Carcinoma, Signet Ring Cell / Q000188:drug therapy / Q000556:secondary; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053778:Thiazolidines / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D008387:Marine Toxins; D053778:Thiazolidines; D020169:Caspases; C037067:latrunculin A