latrunculin-a and Stomach-Neoplasms

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.

Topics: Adenocarcinoma; Animals; Apoptosis; Bridged Bicyclo Compounds, Heterocyclic; Carcinoma, Signet Ring Cell; Caspases; Cell Line, Tumor; Humans; Injections, Intraperitoneal; Male; Marine Toxins; Mice; Mice, Inbred BALB C; Mice, Nude; Peritoneal Neoplasms; Stomach Neoplasms; Thiazolidines; Xenograft Model Antitumor Assays