Cytotoxicity of the hinokitiol-related compounds, gamma-thujaplicin and beta-dolabrin

gamma -Thujaplicin and beta -dolabrin, the constituents of the wood of Thuj opsis dolabrata SIEB. et ZUCC. var. hondai showed strong in vitro cytotoxic effects against the human stomach cancer cell lines KATO-III and Ehrlich's ascites carcinoma. The cytotoxic effects of the two compounds against both tumor cell lines were clear when cell growth was measured by the 3-(4,5-di methylthiazol-2-yl)-2,5-diphenybromide (MTT) method. gamma -Thujaplicin and beta -dolabrin at 0.32 mug/ml inhibited cell growth of human stomach cance r KATO-III by 85 and 67%, and Ehrlich's ascites carcinoma by 91 and 75%, re spectively, There is no large difference in cytotoxicity between these comp ounds, but the activity of gamma -thujaplicin was slightly more potent than that of beta -dolabrin, On the other hand, hinokitiol acetate did not show a cytotoxic effect, suggesting that at least a part of the mechanism of th e cytotoxic effect of hinokitiol-related compounds is due to metal chelatio n between the carbonyl group at C-1 and the hydroxyl group at C-2 in the tr opolone skeleton of these molecules. The acute toxicities [50% lethal dose (LD50) value: intraperitoneal injection, Van der Waedem] of gamma -thujapli cin and beta -dolabrin in mice were 277 mg/kg and 232 mg/kg, respectively.