Latrunculin a has a strong anticancer effect in a peritoneal dissemination model of human gastric cancer in mice.
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.
Konishi
Hiroo
H
Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Kikuchi
Shojiro
S
Ochiai
Toshiya
T
Ikoma
Hisashi
H
Kubota
Takeshi
T
Ichikawa
Daisuke
D
Fujiwara
Hitoshi
H
Okamoto
Kazuma
K
Sakakura
Chouhei
C
Sonoyama
Teruhisa
T
Kokuba
Yukihito
Y
Sasaki
Hiroyuki
H
Matsui
Takeshi
T
Otsuji
Eigo
E
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
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008387:Marine Toxins; D053778:Thiazolidines; D020169:Caspases; C037067:latrunculin A